---
_id: '14502'
abstract:
- lang: eng
text: A precise quantitative description of the ultrastructural characteristics
underlying biological mechanisms is often key to their understanding. This is
particularly true for dynamic extra- and intracellular filamentous assemblies,
playing a role in cell motility, cell integrity, cytokinesis, tissue formation
and maintenance. For example, genetic manipulation or modulation of actin regulatory
proteins frequently manifests in changes of the morphology, dynamics, and ultrastructural
architecture of actin filament-rich cell peripheral structures, such as lamellipodia
or filopodia. However, the observed ultrastructural effects often remain subtle
and require sufficiently large datasets for appropriate quantitative analysis.
The acquisition of such large datasets has been enabled by recent advances in
high-throughput cryo-electron tomography (cryo-ET) methods. This also necessitates
the development of complementary approaches to maximize the extraction of relevant
biological information. We have developed a computational toolbox for the semi-automatic
quantification of segmented and vectorized fila- mentous networks from pre-processed
cryo-electron tomograms, facilitating the analysis and cross-comparison of multiple
experimental conditions. GUI-based components simplify the processing of data
and allow users to obtain a large number of ultrastructural parameters describing
filamentous assemblies. We demonstrate the feasibility of this workflow by analyzing
cryo-ET data of untreated and chemically perturbed branched actin filament networks
and that of parallel actin filament arrays. In principle, the computational toolbox
presented here is applicable for data analysis comprising any type of filaments
in regular (i.e. parallel) or random arrangement. We show that it can ease the
identification of key differences between experimental groups and facilitate the
in-depth analysis of ultrastructural data in a time-efficient manner.
author:
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Behnam
full_name: Amiri, Behnam
last_name: Amiri
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Martin
full_name: Falcke, Martin
last_name: Falcke
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Dimchev GA, Amiri B, Fäßler F, Falcke M, Schur FK. Computational toolbox for
ultrastructural quantitative analysis of filament networks in cryo-ET data. 2023.
doi:10.15479/AT:ISTA:14502
apa: Dimchev, G. A., Amiri, B., Fäßler, F., Falcke, M., & Schur, F. K. (2023).
Computational toolbox for ultrastructural quantitative analysis of filament networks
in cryo-ET data. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:14502
chicago: Dimchev, Georgi A, Behnam Amiri, Florian Fäßler, Martin Falcke, and Florian
KM Schur. “Computational Toolbox for Ultrastructural Quantitative Analysis of
Filament Networks in Cryo-ET Data.” Institute of Science and Technology Austria,
2023. https://doi.org/10.15479/AT:ISTA:14502.
ieee: G. A. Dimchev, B. Amiri, F. Fäßler, M. Falcke, and F. K. Schur, “Computational
toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET
data.” Institute of Science and Technology Austria, 2023.
ista: Dimchev GA, Amiri B, Fäßler F, Falcke M, Schur FK. 2023. Computational toolbox
for ultrastructural quantitative analysis of filament networks in cryo-ET data,
Institute of Science and Technology Austria, 10.15479/AT:ISTA:14502.
mla: Dimchev, Georgi A., et al. Computational Toolbox for Ultrastructural Quantitative
Analysis of Filament Networks in Cryo-ET Data. Institute of Science and Technology
Austria, 2023, doi:10.15479/AT:ISTA:14502.
short: G.A. Dimchev, B. Amiri, F. Fäßler, M. Falcke, F.K. Schur, (2023).
corr_author: '1'
date_created: 2023-11-08T19:40:54Z
date_published: 2023-11-21T00:00:00Z
date_updated: 2025-04-15T08:25:41Z
day: '21'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.15479/AT:ISTA:14502
file:
- access_level: open_access
checksum: a8b9adeb53a4109dea4d5e39fa1acccf
content_type: application/zip
creator: fschur
date_created: 2023-11-08T20:23:07Z
date_updated: 2023-11-08T20:23:07Z
file_id: '14503'
file_name: Computational_Toolbox_v1.2.zip
file_size: 347641117
relation: main_file
success: 1
- access_level: open_access
checksum: 14db2addbfca61a085ba301ed6f2900b
content_type: text/plain
creator: dernst
date_created: 2023-11-21T08:20:23Z
date_updated: 2023-11-21T08:20:23Z
file_id: '14586'
file_name: Readme.txt
file_size: 1522
relation: main_file
success: 1
file_date_updated: 2023-11-21T08:20:23Z
has_accepted_license: '1'
keyword:
- cryo-electron tomography
- actin cytoskeleton
- toolbox
license: https://choosealicense.com/licenses/agpl-3.0/
month: '11'
oa: 1
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
grant_number: P33367
name: Structure and isoform diversity of the Arp2/3 complex
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '10290'
relation: used_for_analysis_in
status: public
status: public
title: Computational toolbox for ultrastructural quantitative analysis of filament
networks in cryo-ET data
tmp:
legal_code_url: https://www.gnu.org/licenses/agpl-3.0.html
name: GNU Affero General Public License v3.0
short: 'GNU AGPLv3 '
type: software
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '12334'
abstract:
- lang: eng
text: Regulation of the Arp2/3 complex is required for productive nucleation of
branched actin networks. An emerging aspect of regulation is the incorporation
of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit
isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity
and branch junction stability. We have combined reverse genetics and cellular
structural biology to describe how ArpC5 and ArpC5L differentially affect cell
migration. Both define the structural stability of ArpC1 in branch junctions and,
in turn, by determining protrusion characteristics, affect protein dynamics and
actin network ultrastructure. ArpC5 isoforms also affect the positioning of members
of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament
elongators, which mediate ArpC5 isoform–specific effects on the actin assembly
level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling
pathway enhancing cell migration.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: "We would like to thank K. von Peinen and B. Denker (Helmholtz Centre
for Infection Research, Braunschweig, Germany) for experimental and technical assistance,
respectively.\r\nThis research was supported by the Scientific Service Units (SSUs)
of ISTA through resources provided by Scientific Computing (SciComp), the Life Science
Facility (LSF), the Imaging and Optics facility (IOF), and the Electron Microscopy
Facility (EMF). We acknowledge support from ISTA and from the Austrian Science Fund
(FWF) (P33367) to F.K.M.S., from the Research Training Group GRK2223 and the Helmholtz
Society to K.R,. and from the Deutsche Forschungsgemeinschaft (DFG) to J.F. and
K.R."
article_number: add6495
article_processing_charge: No
article_type: original
author:
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Manjunath
full_name: Javoor, Manjunath
id: 305ab18b-dc7d-11ea-9b2f-b58195228ea2
last_name: Javoor
orcid: 0000-0003-2311-2112
- first_name: Julia
full_name: Datler, Julia
id: 3B12E2E6-F248-11E8-B48F-1D18A9856A87
last_name: Datler
orcid: 0000-0002-3616-8580
- first_name: Hermann
full_name: Döring, Hermann
last_name: Döring
- first_name: Florian
full_name: Hofer, Florian
id: b9d234ba-9e33-11ed-95b6-cd561df280e6
last_name: Hofer
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Victor-Valentin
full_name: Hodirnau, Victor-Valentin
id: 3661B498-F248-11E8-B48F-1D18A9856A87
last_name: Hodirnau
orcid: 0000-0003-3904-947X
- first_name: Jan
full_name: Faix, Jan
last_name: Faix
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Fäßler F, Javoor M, Datler J, et al. ArpC5 isoforms regulate Arp2/3 complex–dependent
protrusion through differential Ena/VASP positioning. Science Advances.
2023;9(3). doi:10.1126/sciadv.add6495
apa: Fäßler, F., Javoor, M., Datler, J., Döring, H., Hofer, F., Dimchev, G. A.,
… Schur, F. K. (2023). ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion
through differential Ena/VASP positioning. Science Advances. American Association
for the Advancement of Science. https://doi.org/10.1126/sciadv.add6495
chicago: Fäßler, Florian, Manjunath Javoor, Julia Datler, Hermann Döring, Florian
Hofer, Georgi A Dimchev, Victor-Valentin Hodirnau, Jan Faix, Klemens Rottner,
and Florian KM Schur. “ArpC5 Isoforms Regulate Arp2/3 Complex–Dependent Protrusion
through Differential Ena/VASP Positioning.” Science Advances. American
Association for the Advancement of Science, 2023. https://doi.org/10.1126/sciadv.add6495.
ieee: F. Fäßler et al., “ArpC5 isoforms regulate Arp2/3 complex–dependent
protrusion through differential Ena/VASP positioning,” Science Advances,
vol. 9, no. 3. American Association for the Advancement of Science, 2023.
ista: Fäßler F, Javoor M, Datler J, Döring H, Hofer F, Dimchev GA, Hodirnau V-V,
Faix J, Rottner K, Schur FK. 2023. ArpC5 isoforms regulate Arp2/3 complex–dependent
protrusion through differential Ena/VASP positioning. Science Advances. 9(3),
add6495.
mla: Fäßler, Florian, et al. “ArpC5 Isoforms Regulate Arp2/3 Complex–Dependent Protrusion
through Differential Ena/VASP Positioning.” Science Advances, vol. 9, no.
3, add6495, American Association for the Advancement of Science, 2023, doi:10.1126/sciadv.add6495.
short: F. Fäßler, M. Javoor, J. Datler, H. Döring, F. Hofer, G.A. Dimchev, V.-V.
Hodirnau, J. Faix, K. Rottner, F.K. Schur, Science Advances 9 (2023).
corr_author: '1'
date_created: 2023-01-23T07:26:42Z
date_published: 2023-01-20T00:00:00Z
date_updated: 2026-04-07T12:59:44Z
day: '20'
ddc:
- '570'
department:
- _id: FlSc
- _id: EM-Fac
doi: 10.1126/sciadv.add6495
external_id:
isi:
- '000964550100015'
pmid:
- '36662867'
file:
- access_level: open_access
checksum: ce81a6d0b84170e5e8c62f6acfa15d9e
content_type: application/pdf
creator: dernst
date_created: 2023-01-23T07:45:54Z
date_updated: 2023-01-23T07:45:54Z
file_id: '12335'
file_name: 2023_ScienceAdvances_Faessler.pdf
file_size: 1756234
relation: main_file
success: 1
file_date_updated: 2023-01-23T07:45:54Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '3'
keyword:
- Multidisciplinary
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
grant_number: P33367
name: Structure and isoform diversity of the Arp2/3 complex
publication: Science Advances
publication_identifier:
issn:
- 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
record:
- id: '14562'
relation: research_data
status: public
- id: '18766'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion through differential
Ena/VASP positioning
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2023'
...
---
_id: '10290'
abstract:
- lang: eng
text: A precise quantitative description of the ultrastructural characteristics
underlying biological mechanisms is often key to their understanding. This is
particularly true for dynamic extra- and intracellular filamentous assemblies,
playing a role in cell motility, cell integrity, cytokinesis, tissue formation
and maintenance. For example, genetic manipulation or modulation of actin regulatory
proteins frequently manifests in changes of the morphology, dynamics, and ultrastructural
architecture of actin filament-rich cell peripheral structures, such as lamellipodia
or filopodia. However, the observed ultrastructural effects often remain subtle
and require sufficiently large datasets for appropriate quantitative analysis.
The acquisition of such large datasets has been enabled by recent advances in
high-throughput cryo-electron tomography (cryo-ET) methods. This also necessitates
the development of complementary approaches to maximize the extraction of relevant
biological information. We have developed a computational toolbox for the semi-automatic
quantification of segmented and vectorized filamentous networks from pre-processed
cryo-electron tomograms, facilitating the analysis and cross-comparison of multiple
experimental conditions. GUI-based components simplify the processing of data
and allow users to obtain a large number of ultrastructural parameters describing
filamentous assemblies. We demonstrate the feasibility of this workflow by analyzing
cryo-ET data of untreated and chemically perturbed branched actin filament networks
and that of parallel actin filament arrays. In principle, the computational toolbox
presented here is applicable for data analysis comprising any type of filaments
in regular (i.e. parallel) or random arrangement. We show that it can ease the
identification of key differences between experimental groups and facilitate the
in-depth analysis of ultrastructural data in a time-efficient manner.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: 'This research was supported by the Scientific Service Units (SSUs)
of IST Austria through resources provided by Scientific Computing (SciComp), the
Life Science Facility (LSF), the BioImaging Facility (BIF), and the Electron Microscopy
Facility (EMF). We also thank Victor-Valentin Hodirnau for help with cryo-ET data
acquisition. The authors acknowledge support from IST Austria and from the Austrian
Science Fund (FWF): M02495 to G.D. and Austrian Science Fund (FWF): P33367 to F.K.M.S.'
article_number: '107808'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Behnam
full_name: Amiri, Behnam
last_name: Amiri
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Martin
full_name: Falcke, Martin
last_name: Falcke
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Dimchev GA, Amiri B, Fäßler F, Falcke M, Schur FK. Computational toolbox for
ultrastructural quantitative analysis of filament networks in cryo-ET data. Journal
of Structural Biology. 2021;213(4). doi:10.1016/j.jsb.2021.107808
apa: Dimchev, G. A., Amiri, B., Fäßler, F., Falcke, M., & Schur, F. K. (2021).
Computational toolbox for ultrastructural quantitative analysis of filament networks
in cryo-ET data. Journal of Structural Biology. Elsevier . https://doi.org/10.1016/j.jsb.2021.107808
chicago: Dimchev, Georgi A, Behnam Amiri, Florian Fäßler, Martin Falcke, and Florian
KM Schur. “Computational Toolbox for Ultrastructural Quantitative Analysis of
Filament Networks in Cryo-ET Data.” Journal of Structural Biology. Elsevier
, 2021. https://doi.org/10.1016/j.jsb.2021.107808.
ieee: G. A. Dimchev, B. Amiri, F. Fäßler, M. Falcke, and F. K. Schur, “Computational
toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET
data,” Journal of Structural Biology, vol. 213, no. 4. Elsevier , 2021.
ista: Dimchev GA, Amiri B, Fäßler F, Falcke M, Schur FK. 2021. Computational toolbox
for ultrastructural quantitative analysis of filament networks in cryo-ET data.
Journal of Structural Biology. 213(4), 107808.
mla: Dimchev, Georgi A., et al. “Computational Toolbox for Ultrastructural Quantitative
Analysis of Filament Networks in Cryo-ET Data.” Journal of Structural Biology,
vol. 213, no. 4, 107808, Elsevier , 2021, doi:10.1016/j.jsb.2021.107808.
short: G.A. Dimchev, B. Amiri, F. Fäßler, M. Falcke, F.K. Schur, Journal of Structural
Biology 213 (2021).
corr_author: '1'
date_created: 2021-11-15T12:21:42Z
date_published: 2021-11-03T00:00:00Z
date_updated: 2025-04-15T08:25:41Z
day: '03'
ddc:
- '572'
department:
- _id: FlSc
doi: 10.1016/j.jsb.2021.107808
external_id:
isi:
- '000720259500002'
file:
- access_level: open_access
checksum: 6b209e4d44775d4e02b50f78982c15fa
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-15T13:11:27Z
date_updated: 2021-11-15T13:11:27Z
file_id: '10291'
file_name: 2021_JournalStructBiol_Dimchev.pdf
file_size: 16818304
relation: main_file
success: 1
file_date_updated: 2021-11-15T13:11:27Z
has_accepted_license: '1'
intvolume: ' 213'
isi: 1
issue: '4'
keyword:
- Structural Biology
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
grant_number: P33367
name: Structure and isoform diversity of the Arp2/3 complex
- _id: 2674F658-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02495
name: Protein structure and function in filopodia across scales
publication: Journal of Structural Biology
publication_identifier:
issn:
- 1047-8477
publication_status: published
publisher: 'Elsevier '
quality_controlled: '1'
related_material:
record:
- id: '14502'
relation: software
status: public
scopus_import: '1'
status: public
title: Computational toolbox for ultrastructural quantitative analysis of filament
networks in cryo-ET data
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 213
year: '2021'
...
---
_id: '9429'
abstract:
- lang: eng
text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency
leads to motor coordination deficits as well as ASD-relevant social and cognitive
impairments. However, induction of Cul3 haploinsufficiency later in life does
not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during
a critical developmental window. Here we show that Cul3 is essential to regulate
neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice
display cortical lamination abnormalities. At the molecular level, we found that
Cul3 controls neuronal migration by tightly regulating the amount of Plastin3
(Pls3), a previously unrecognized player of neural migration. Furthermore, we
found that Pls3 cell-autonomously regulates cell migration by regulating actin
cytoskeleton organization, and its levels are inversely proportional to neural
migration speed. Finally, we provide evidence that cellular phenotypes associated
with autism-linked gene haploinsufficiency can be rescued by transcriptional activation
of the intact allele in vitro, offering a proof of concept for a potential therapeutic
approach for ASDs.
acknowledged_ssus:
- _id: PreCl
acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A.
Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the
management of our animal colony, as well as M. Schunn and the Preclinical Facility
team for technical assistance. We thank K. Heesom and her team at the University
of Bristol Proteomics Facility for the proteomics sample preparation, data generation,
and analysis support. We thank Y. B. Simon for kindly providing the plasmid for
lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration
and the fruitful discussions. This work was supported by the ISTPlus postdoctoral
fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon
2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by
the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D
(I3600-B27).
article_number: '3058'
article_processing_charge: No
article_type: original
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Zoe
full_name: Dobler, Zoe
id: D23090A2-9057-11EA-883A-A8396FC7A38F
last_name: Dobler
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
homeostasis and cell migration during a critical window of brain development.
Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x
apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A.,
Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-021-23123-x
chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton
Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.”
Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.
ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development,” Nature Communications,
vol. 12, no. 1. Springer Nature, 2021.
ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer
CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino
G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during
a critical window of brain development. Nature Communications. 12(1), 3058.
mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
and Cell Migration during a Critical Window of Brain Development.” Nature Communications,
vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.
short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas,
C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur,
J.G. Danzl, G. Novarino, Nature Communications 12 (2021).
corr_author: '1'
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2026-05-05T22:31:00Z
day: '24'
ddc:
- '572'
department:
- _id: GaNo
- _id: JoDa
- _id: FlSc
- _id: MiSi
- _id: LifeSc
- _id: Bio
doi: 10.1038/s41467-021-23123-x
ec_funded: 1
external_id:
isi:
- '000658769900010'
file:
- access_level: open_access
checksum: 337e0f7959c35ec959984cacdcb472ba
content_type: application/pdf
creator: kschuh
date_created: 2021-05-28T12:39:43Z
date_updated: 2021-05-28T12:39:43Z
file_id: '9430'
file_name: 2021_NatureCommunications_Morandell.pdf
file_size: 9358599
relation: main_file
success: 1
file_date_updated: 2021-05-28T12:39:43Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F7807
name: Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem
cells in autism and epilepsy
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: press_release
url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/
record:
- id: '19557'
relation: dissertation_contains
status: public
- id: '7800'
relation: earlier_version
status: public
- id: '12401'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
critical window of brain development
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '15286'
article_processing_charge: No
article_type: original
author:
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Victor-Valentin
full_name: Hodirnau, Victor-Valentin
id: 3661B498-F248-11E8-B48F-1D18A9856A87
last_name: Hodirnau
orcid: 0000-0003-3904-947X
- first_name: Bettina
full_name: Zens, Bettina
id: 45FD126C-F248-11E8-B48F-1D18A9856A87
last_name: Zens
orcid: 0000-0002-9561-1239
- first_name: Christoph
full_name: Möhl, Christoph
last_name: Möhl
- first_name: Frank
full_name: Bradke, Frank
last_name: Bradke
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Fäßler F, Dimchev GA, Hodirnau V-V, et al. Cryo-electron tomography workflows
for quantitative analysis of actin networks involved in cell migration. Microscopy
and Microanalysis. 2020;26(S2):2518-2519. doi:10.1017/s1431927620021881
apa: Fäßler, F., Dimchev, G. A., Hodirnau, V.-V., Zens, B., Möhl, C., Bradke, F.,
& Schur, F. K. (2020). Cryo-electron tomography workflows for quantitative
analysis of actin networks involved in cell migration. Microscopy and Microanalysis.
Oxford University Press. https://doi.org/10.1017/s1431927620021881
chicago: Fäßler, Florian, Georgi A Dimchev, Victor-Valentin Hodirnau, Bettina Zens,
Christoph Möhl, Frank Bradke, and Florian KM Schur. “Cryo-Electron Tomography
Workflows for Quantitative Analysis of Actin Networks Involved in Cell Migration.”
Microscopy and Microanalysis. Oxford University Press, 2020. https://doi.org/10.1017/s1431927620021881.
ieee: F. Fäßler et al., “Cryo-electron tomography workflows for quantitative
analysis of actin networks involved in cell migration,” Microscopy and Microanalysis,
vol. 26, no. S2. Oxford University Press, pp. 2518–2519, 2020.
ista: Fäßler F, Dimchev GA, Hodirnau V-V, Zens B, Möhl C, Bradke F, Schur FK. 2020.
Cryo-electron tomography workflows for quantitative analysis of actin networks
involved in cell migration. Microscopy and Microanalysis. 26(S2), 2518–2519.
mla: Fäßler, Florian, et al. “Cryo-Electron Tomography Workflows for Quantitative
Analysis of Actin Networks Involved in Cell Migration.” Microscopy and Microanalysis,
vol. 26, no. S2, Oxford University Press, 2020, pp. 2518–19, doi:10.1017/s1431927620021881.
short: F. Fäßler, G.A. Dimchev, V.-V. Hodirnau, B. Zens, C. Möhl, F. Bradke, F.K.
Schur, Microscopy and Microanalysis 26 (2020) 2518–2519.
corr_author: '1'
date_created: 2024-04-03T09:40:11Z
date_published: 2020-08-01T00:00:00Z
date_updated: 2024-10-09T21:08:43Z
day: '01'
department:
- _id: FlSc
- _id: EM-Fac
doi: 10.1017/s1431927620021881
intvolume: ' 26'
issue: S2
keyword:
- Instrumentation
language:
- iso: eng
month: '08'
oa_version: None
page: 2518-2519
publication: Microscopy and Microanalysis
publication_identifier:
eissn:
- 1435-8115
issn:
- 1431-9276
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
status: public
title: Cryo-electron tomography workflows for quantitative analysis of actin networks
involved in cell migration
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 26
year: '2020'
...
---
_id: '8971'
abstract:
- lang: eng
text: The actin-related protein (Arp)2/3 complex nucleates branched actin filament
networks pivotal for cell migration, endocytosis and pathogen infection. Its activation
is tightly regulated and involves complex structural rearrangements and actin
filament binding, which are yet to be understood. Here, we report a 9.0 Å resolution
structure of the actin filament Arp2/3 complex branch junction in cells using
cryo-electron tomography and subtomogram averaging. This allows us to generate
an accurate model of the active Arp2/3 complex in the branch junction and its
interaction with actin filaments. Notably, our model reveals a previously undescribed
set of interactions of the Arp2/3 complex with the mother filament, significantly
different to the previous branch junction model. Our structure also indicates
a central role for the ArpC3 subunit in stabilizing the active conformation.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: "This research was supported by the Scientific Service Units (SSUs)
of IST Austria through resources provided by Scientific Computing (SciComp), the
Life Science Facility (LSF), the BioImaging Facility (BIF), and the Electron Microscopy
Facility (EMF). We also thank Dimitry Tegunov (MPI for Biophysical Chemistry) for
helpful discussions\r\nabout the M software, and Michael Sixt (IST Austria) and
Klemens Rottner (Technical University Braunschweig, HZI Braunschweig) for critical
reading of the manuscript. We also thank Gregory Voth (University of Chicago) for
providing us the MD-derived branch junction model for comparison. The authors acknowledge
support from IST Austria and from the Austrian Science Fund (FWF): M02495 to G.D.
and Austrian Science Fund (FWF): P33367 to F.K.M.S. "
article_number: '6437'
article_processing_charge: No
article_type: original
author:
- first_name: Florian
full_name: Fäßler, Florian
id: 404F5528-F248-11E8-B48F-1D18A9856A87
last_name: Fäßler
orcid: 0000-0001-7149-769X
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Victor-Valentin
full_name: Hodirnau, Victor-Valentin
id: 3661B498-F248-11E8-B48F-1D18A9856A87
last_name: Hodirnau
orcid: 0000-0003-3904-947X
- first_name: William
full_name: Wan, William
last_name: Wan
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
citation:
ama: Fäßler F, Dimchev GA, Hodirnau V-V, Wan W, Schur FK. Cryo-electron tomography
structure of Arp2/3 complex in cells reveals new insights into the branch junction.
Nature Communications. 2020;11. doi:10.1038/s41467-020-20286-x
apa: Fäßler, F., Dimchev, G. A., Hodirnau, V.-V., Wan, W., & Schur, F. K. (2020).
Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights
into the branch junction. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-020-20286-x
chicago: Fäßler, Florian, Georgi A Dimchev, Victor-Valentin Hodirnau, William Wan,
and Florian KM Schur. “Cryo-Electron Tomography Structure of Arp2/3 Complex in
Cells Reveals New Insights into the Branch Junction.” Nature Communications.
Springer Nature, 2020. https://doi.org/10.1038/s41467-020-20286-x.
ieee: F. Fäßler, G. A. Dimchev, V.-V. Hodirnau, W. Wan, and F. K. Schur, “Cryo-electron
tomography structure of Arp2/3 complex in cells reveals new insights into the
branch junction,” Nature Communications, vol. 11. Springer Nature, 2020.
ista: Fäßler F, Dimchev GA, Hodirnau V-V, Wan W, Schur FK. 2020. Cryo-electron tomography
structure of Arp2/3 complex in cells reveals new insights into the branch junction.
Nature Communications. 11, 6437.
mla: Fäßler, Florian, et al. “Cryo-Electron Tomography Structure of Arp2/3 Complex
in Cells Reveals New Insights into the Branch Junction.” Nature Communications,
vol. 11, 6437, Springer Nature, 2020, doi:10.1038/s41467-020-20286-x.
short: F. Fäßler, G.A. Dimchev, V.-V. Hodirnau, W. Wan, F.K. Schur, Nature Communications
11 (2020).
corr_author: '1'
date_created: 2020-12-23T08:25:45Z
date_published: 2020-12-22T00:00:00Z
date_updated: 2025-04-15T07:52:12Z
day: '22'
ddc:
- '570'
department:
- _id: FlSc
- _id: EM-Fac
doi: 10.1038/s41467-020-20286-x
external_id:
isi:
- '000603078000003'
file:
- access_level: open_access
checksum: 55d43ea0061cc4027ba45e966e1db8cc
content_type: application/pdf
creator: dernst
date_created: 2020-12-28T08:16:10Z
date_updated: 2020-12-28T08:16:10Z
file_id: '8975'
file_name: 2020_NatureComm_Faessler.pdf
file_size: 3958727
relation: main_file
success: 1
file_date_updated: 2020-12-28T08:16:10Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
keyword:
- General Biochemistry
- Genetics and Molecular Biology
- General Physics and Astronomy
- General Chemistry
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
project:
- _id: 9B954C5C-BA93-11EA-9121-9846C619BF3A
grant_number: P33367
name: Structure and isoform diversity of the Arp2/3 complex
- _id: 2674F658-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02495
name: Protein structure and function in filopodia across scales
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/cutting-edge-technology-reveals-structures-within-cells/
scopus_import: '1'
status: public
title: Cryo-electron tomography structure of Arp2/3 complex in cells reveals new insights
into the branch junction
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...
---
_id: '7909'
abstract:
- lang: eng
text: Cell migration entails networks and bundles of actin filaments termed lamellipodia
and microspikes or filopodia, respectively, as well as focal adhesions, all of
which recruit Ena/VASP family members hitherto thought to antagonize efficient
cell motility. However, we find these proteins to act as positive regulators of
migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP
proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture,
as evidenced by changed network geometry as well as reduction of filament length
and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping
protein accumulation. Loss of Ena/VASP function also abolished the formation of
microspikes normally embedded in lamellipodia, but not of filopodia capable of
emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated
adhesion accompanied by reduced traction forces exerted through these structures.
Our data thus uncover novel Ena/VASP functions of these actin polymerases that
are fully consistent with their promotion of cell migration.
article_number: e55351
article_processing_charge: No
article_type: original
author:
- first_name: Julia
full_name: Damiano-Guercio, Julia
last_name: Damiano-Guercio
- first_name: Laëtitia
full_name: Kurzawa, Laëtitia
last_name: Kurzawa
- first_name: Jan
full_name: Müller, Jan
id: AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D
last_name: Müller
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Matthias
full_name: Schaks, Matthias
last_name: Schaks
- first_name: Maria
full_name: Nemethova, Maria
id: 34E27F1C-F248-11E8-B48F-1D18A9856A87
last_name: Nemethova
- first_name: Thomas
full_name: Pokrant, Thomas
last_name: Pokrant
- first_name: Stefan
full_name: Brühmann, Stefan
last_name: Brühmann
- first_name: Joern
full_name: Linkner, Joern
last_name: Linkner
- first_name: Laurent
full_name: Blanchoin, Laurent
last_name: Blanchoin
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
- first_name: Jan
full_name: Faix, Jan
last_name: Faix
citation:
ama: Damiano-Guercio J, Kurzawa L, Müller J, et al. Loss of Ena/VASP interferes
with lamellipodium architecture, motility and integrin-dependent adhesion. eLife.
2020;9. doi:10.7554/eLife.55351
apa: Damiano-Guercio, J., Kurzawa, L., Müller, J., Dimchev, G. A., Schaks, M., Nemethova,
M., … Faix, J. (2020). Loss of Ena/VASP interferes with lamellipodium architecture,
motility and integrin-dependent adhesion. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.55351
chicago: Damiano-Guercio, Julia, Laëtitia Kurzawa, Jan Müller, Georgi A Dimchev,
Matthias Schaks, Maria Nemethova, Thomas Pokrant, et al. “Loss of Ena/VASP Interferes
with Lamellipodium Architecture, Motility and Integrin-Dependent Adhesion.” ELife.
eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.55351.
ieee: J. Damiano-Guercio et al., “Loss of Ena/VASP interferes with lamellipodium
architecture, motility and integrin-dependent adhesion,” eLife, vol. 9.
eLife Sciences Publications, 2020.
ista: Damiano-Guercio J, Kurzawa L, Müller J, Dimchev GA, Schaks M, Nemethova M,
Pokrant T, Brühmann S, Linkner J, Blanchoin L, Sixt MK, Rottner K, Faix J. 2020.
Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent
adhesion. eLife. 9, e55351.
mla: Damiano-Guercio, Julia, et al. “Loss of Ena/VASP Interferes with Lamellipodium
Architecture, Motility and Integrin-Dependent Adhesion.” ELife, vol. 9,
e55351, eLife Sciences Publications, 2020, doi:10.7554/eLife.55351.
short: J. Damiano-Guercio, L. Kurzawa, J. Müller, G.A. Dimchev, M. Schaks, M. Nemethova,
T. Pokrant, S. Brühmann, J. Linkner, L. Blanchoin, M.K. Sixt, K. Rottner, J. Faix,
ELife 9 (2020).
date_created: 2020-05-31T22:00:49Z
date_published: 2020-05-11T00:00:00Z
date_updated: 2026-04-02T14:32:12Z
day: '11'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.7554/eLife.55351
ec_funded: 1
external_id:
isi:
- '000537208000001'
pmid:
- '32391788'
file:
- access_level: open_access
checksum: d33bd4441b9a0195718ce1ba5d2c48a6
content_type: application/pdf
creator: dernst
date_created: 2020-06-02T10:35:37Z
date_updated: 2020-07-14T12:48:05Z
file_id: '7914'
file_name: 2020_eLife_Damiano_Guercio.pdf
file_size: 10535713
relation: main_file
file_date_updated: 2020-07-14T12:48:05Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent
adhesion
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 9
year: '2020'
...
---
_id: '8434'
abstract:
- lang: eng
text: 'Efficient migration on adhesive surfaces involves the protrusion of lamellipodial
actin networks and their subsequent stabilization by nascent adhesions. The actin-binding
protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium
protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin
filaments and by interacting with the WAVE regulatory complex, an activator of
the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we
demonstrate that genetic ablation of Lpd compromises protrusion efficiency and
coincident cell migration without altering essential parameters of lamellipodia,
including their maximal rate of forward advancement and actin polymerization.
We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated
Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover,
computer-aided analysis of cell-edge morphodynamics on B16-F1 cell lamellipodia
revealed that loss of Lpd correlates with reduced temporal protrusion maintenance
as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes
protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction
and membrane ruffling.This article has an associated First Person interview with
the first author of the paper. '
acknowledgement: This work was supported in part by Deutsche Forschungsgemeinschaft
(DFG)[GRK2223/1, RO2414/5-1 (to K.R.), FA350/11-1 (to M.F.) and FA330/11-1 (to J.F.)],as
well as by intramural funding from the Helmholtz Association (to T.E.B.S. andK.R.).
G.D. was additionally funded by the Austrian Science Fund (FWF) LiseMeitner Program
[M-2495]. A.C.H. and M.W. are supported by the Francis CrickInstitute, which receives
its core funding from Cancer Research UK [FC001209], theMedical Research Council
[FC001209] and the Wellcome Trust [FC001209]. M.K. issupported by the Biotechnology
and Biological Sciences Research Council [BB/F011431/1, BB/J000590/1, BB/N000226/1].
Deposited in PMC for release after 6months.
article_number: jcs239020
article_processing_charge: No
article_type: original
author:
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Behnam
full_name: Amiri, Behnam
last_name: Amiri
- first_name: Ashley C.
full_name: Humphries, Ashley C.
last_name: Humphries
- first_name: Matthias
full_name: Schaks, Matthias
last_name: Schaks
- first_name: Vanessa
full_name: Dimchev, Vanessa
last_name: Dimchev
- first_name: Theresia E. B.
full_name: Stradal, Theresia E. B.
last_name: Stradal
- first_name: Jan
full_name: Faix, Jan
last_name: Faix
- first_name: Matthias
full_name: Krause, Matthias
last_name: Krause
- first_name: Michael
full_name: Way, Michael
last_name: Way
- first_name: Martin
full_name: Falcke, Martin
last_name: Falcke
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
citation:
ama: Dimchev GA, Amiri B, Humphries AC, et al. Lamellipodin tunes cell migration
by stabilizing protrusions and promoting adhesion formation. Journal of Cell
Science. 2020;133(7). doi:10.1242/jcs.239020
apa: Dimchev, G. A., Amiri, B., Humphries, A. C., Schaks, M., Dimchev, V., Stradal,
T. E. B., … Rottner, K. (2020). Lamellipodin tunes cell migration by stabilizing
protrusions and promoting adhesion formation. Journal of Cell Science.
The Company of Biologists. https://doi.org/10.1242/jcs.239020
chicago: Dimchev, Georgi A, Behnam Amiri, Ashley C. Humphries, Matthias Schaks,
Vanessa Dimchev, Theresia E. B. Stradal, Jan Faix, et al. “Lamellipodin Tunes
Cell Migration by Stabilizing Protrusions and Promoting Adhesion Formation.” Journal
of Cell Science. The Company of Biologists, 2020. https://doi.org/10.1242/jcs.239020.
ieee: G. A. Dimchev et al., “Lamellipodin tunes cell migration by stabilizing
protrusions and promoting adhesion formation,” Journal of Cell Science,
vol. 133, no. 7. The Company of Biologists, 2020.
ista: Dimchev GA, Amiri B, Humphries AC, Schaks M, Dimchev V, Stradal TEB, Faix
J, Krause M, Way M, Falcke M, Rottner K. 2020. Lamellipodin tunes cell migration
by stabilizing protrusions and promoting adhesion formation. Journal of Cell Science.
133(7), jcs239020.
mla: Dimchev, Georgi A., et al. “Lamellipodin Tunes Cell Migration by Stabilizing
Protrusions and Promoting Adhesion Formation.” Journal of Cell Science,
vol. 133, no. 7, jcs239020, The Company of Biologists, 2020, doi:10.1242/jcs.239020.
short: G.A. Dimchev, B. Amiri, A.C. Humphries, M. Schaks, V. Dimchev, T.E.B. Stradal,
J. Faix, M. Krause, M. Way, M. Falcke, K. Rottner, Journal of Cell Science 133
(2020).
date_created: 2020-09-17T14:00:33Z
date_published: 2020-04-09T00:00:00Z
date_updated: 2025-04-15T07:52:13Z
day: '09'
ddc:
- '570'
department:
- _id: FlSc
doi: 10.1242/jcs.239020
external_id:
isi:
- '000534387800005'
pmid:
- ' 32094266'
file:
- access_level: open_access
checksum: ba917e551acc4ece2884b751434df9ae
content_type: application/pdf
creator: dernst
date_created: 2020-09-17T14:07:51Z
date_updated: 2020-10-11T22:30:02Z
embargo: 2020-10-10
file_id: '8435'
file_name: 2020_JournalCellScience_Dimchev.pdf
file_size: 13493302
relation: main_file
file_date_updated: 2020-10-11T22:30:02Z
has_accepted_license: '1'
intvolume: ' 133'
isi: 1
issue: '7'
keyword:
- Cell Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2674F658-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02495
name: Protein structure and function in filopodia across scales
publication: Journal of Cell Science
publication_identifier:
eissn:
- 1477-9137
issn:
- 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Lamellipodin tunes cell migration by stabilizing protrusions and promoting
adhesion formation
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 133
year: '2020'
...
---
_id: '811'
abstract:
- lang: eng
text: Cell migration is commonly accompanied by protrusion of membrane ruffles and
lamellipodia. In two-dimensional migration, protrusion of these thin sheets of
cytoplasm is considered relevant to both exploration of new space and initiation
of nascent adhesion to the substratum. Lamellipodium formation can be potently
stimulated by Rho GTPases of the Rac subfamily, but alsoby RhoG or Cdc42. Here
we describe viable fibroblast cell lines geneticallydeficient for Rac1 that lack
detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent
lamellipodia, but these structures were restored by expression of either Rac subfamily
member, but not by Cdc42 or RhoG. Cells deficient in Rac showed strong reduction
in wound closure and random cell migration and a notable loss of sensitivity to
a chemotactic gradient. Despite these defects, Rac-deficient cells were able to
spread, formed filopodia and established focal adhesions. Spreading in these cells
was achieved by the extension of filopodia followed by the advancement of cytoplasmic
veils between them. The number and size of focal adhesions as well as their intensity
were largely unaffected by genetic removal of Rac1. However, Rac deficiency increased
the mobility of different components in focal adhesions, potentially explaining
how Rac - although not essential - can contribute to focal adhesion assembly.
Together, our data demonstrate that Rac signaling is essential for lamellipodium
protrusion and for efficient cell migration, but not for spreading or filopodium
formation. Our findings also suggest that Rac GTPases are crucial to the establishment
or maintenance of polarity in chemotactic migration.
acknowledgement: |-
This work was supported in part by the Deutsche Forschungsgemeinschaft [grants within programs SFB621 to K.R., and FOR629 and SFB629 to T.E.B.S.]. Deposited in PMC for immediate release.
We thank Brigitte Denker and Gerd Landsberg for excellent technical assistance. We are grateful to Robert Geffers (HZI Braunschweig, Germany) for microarray analyses and to Mirko Himmel (UKE Hamburg, Germany) for valuable advice on FRAP analysis.
author:
- first_name: Anika
full_name: Steffen, Anika
last_name: Steffen
- first_name: Markus
full_name: Ladwein, Markus
last_name: Ladwein
- first_name: Georgi A
full_name: Georgi Dimchev
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
- first_name: Anke
full_name: Hein, Anke
last_name: Hein
- first_name: Lisa
full_name: Schwenkmezger, Lisa
last_name: Schwenkmezger
- first_name: Stefan
full_name: Arens, Stefan
last_name: Arens
- first_name: Kathrin
full_name: Ladwein, Kathrin I
last_name: Ladwein
- first_name: J.
full_name: Holleboom, J. Margit
last_name: Holleboom
- first_name: Florian
full_name: Florian Schur
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: John
full_name: Small, John V
last_name: Small
- first_name: Janett
full_name: Schwarz, Janett
last_name: Schwarz
- first_name: Ralf
full_name: Gerhard, Ralf
last_name: Gerhard
- first_name: Jan
full_name: Faix, Jan
last_name: Faix
- first_name: Theresia
full_name: Stradal, Theresia E
last_name: Stradal
- first_name: Cord
full_name: Brakebusch, Cord H
last_name: Brakebusch
- first_name: Klemens
full_name: Rottner, Klemens
last_name: Rottner
citation:
ama: Steffen A, Ladwein M, Dimchev GA, et al. Rac function is crucial for cell migration
but is not required for spreading and focal adhesion formation. Journal of
Cell Science. 2013;126(20):4572-4588. doi:10.1242/jcs.118232
apa: Steffen, A., Ladwein, M., Dimchev, G. A., Hein, A., Schwenkmezger, L., Arens,
S., … Rottner, K. (2013). Rac function is crucial for cell migration but is not
required for spreading and focal adhesion formation. Journal of Cell Science.
Company of Biologists. https://doi.org/10.1242/jcs.118232
chicago: Steffen, Anika, Markus Ladwein, Georgi A Dimchev, Anke Hein, Lisa Schwenkmezger,
Stefan Arens, Kathrin Ladwein, et al. “Rac Function Is Crucial for Cell Migration
but Is Not Required for Spreading and Focal Adhesion Formation.” Journal of
Cell Science. Company of Biologists, 2013. https://doi.org/10.1242/jcs.118232.
ieee: A. Steffen et al., “Rac function is crucial for cell migration but
is not required for spreading and focal adhesion formation,” Journal of Cell
Science, vol. 126, no. 20. Company of Biologists, pp. 4572–4588, 2013.
ista: Steffen A, Ladwein M, Dimchev GA, Hein A, Schwenkmezger L, Arens S, Ladwein
K, Holleboom J, Schur FK, Small J, Schwarz J, Gerhard R, Faix J, Stradal T, Brakebusch
C, Rottner K. 2013. Rac function is crucial for cell migration but is not required
for spreading and focal adhesion formation. Journal of Cell Science. 126(20),
4572–4588.
mla: Steffen, Anika, et al. “Rac Function Is Crucial for Cell Migration but Is Not
Required for Spreading and Focal Adhesion Formation.” Journal of Cell Science,
vol. 126, no. 20, Company of Biologists, 2013, pp. 4572–88, doi:10.1242/jcs.118232.
short: A. Steffen, M. Ladwein, G.A. Dimchev, A. Hein, L. Schwenkmezger, S. Arens,
K. Ladwein, J. Holleboom, F.K. Schur, J. Small, J. Schwarz, R. Gerhard, J. Faix,
T. Stradal, C. Brakebusch, K. Rottner, Journal of Cell Science 126 (2013) 4572–4588.
date_created: 2018-12-11T11:48:38Z
date_published: 2013-01-01T00:00:00Z
date_updated: 2021-01-12T08:16:57Z
day: '01'
doi: 10.1242/jcs.118232
extern: 1
intvolume: ' 126'
issue: '20'
month: '01'
page: 4572 - 4588
publication: Journal of Cell Science
publication_status: published
publisher: Company of Biologists
publist_id: '6840'
quality_controlled: 0
status: public
title: Rac function is crucial for cell migration but is not required for spreading
and focal adhesion formation
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
volume: 126
year: '2013'
...