---
_id: '491'
abstract:
- lang: eng
text: In their search for antigens, lymphocytes continuously shuttle among blood
vessels, lymph vessels, and lymphatic tissues. Chemokines mediate entry of lymphocytes
into lymphatic tissues, and sphingosine 1-phosphate (S1P) promotes localization
of lymphocytes to the vasculature. Both signals are sensed through G protein-coupled
receptors (GPCRs). Most GPCRs undergo ligand-dependent homologous receptor desensitization,
a process that decreases their signaling output after previous exposure to high
ligand concentration. Such desensitization can explain why lymphocytes do not
take an intermediate position between two signals but rather oscillate between
them. The desensitization of S1P receptor 1 (S1PR1) is mediated by GPCR kinase
2 (GRK2). Deletion of GRK2 in lymphocytes compromises desensitization by high
vascular S1P concentrations, thereby reducing responsiveness to the chemokine
signal and trapping the cells in the vascular compartment. The desensitization
kinetics of S1PR1 allows lymphocytes to dynamically shuttle between vasculature
and lymphatic tissue, although the positional information in both compartments
is static.
article_number: pe43
article_processing_charge: No
author:
- first_name: Alexander
full_name: Eichner, Alexander
id: 4DFA52AE-F248-11E8-B48F-1D18A9856A87
last_name: Eichner
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Eichner A, Sixt MK. Setting the clock for recirculating lymphocytes. Science
Signaling. 2011;4(198). doi:10.1126/scisignal.2002617
apa: Eichner, A., & Sixt, M. K. (2011). Setting the clock for recirculating
lymphocytes. Science Signaling. American Association for the Advancement
of Science. https://doi.org/10.1126/scisignal.2002617
chicago: Eichner, Alexander, and Michael K Sixt. “Setting the Clock for Recirculating
Lymphocytes.” Science Signaling. American Association for the Advancement
of Science, 2011. https://doi.org/10.1126/scisignal.2002617.
ieee: A. Eichner and M. K. Sixt, “Setting the clock for recirculating lymphocytes,”
Science Signaling, vol. 4, no. 198. American Association for the Advancement
of Science, 2011.
ista: Eichner A, Sixt MK. 2011. Setting the clock for recirculating lymphocytes.
Science Signaling. 4(198), pe43.
mla: Eichner, Alexander, and Michael K. Sixt. “Setting the Clock for Recirculating
Lymphocytes.” Science Signaling, vol. 4, no. 198, pe43, American Association
for the Advancement of Science, 2011, doi:10.1126/scisignal.2002617.
short: A. Eichner, M.K. Sixt, Science Signaling 4 (2011).
corr_author: '1'
date_created: 2018-12-11T11:46:46Z
date_published: 2011-11-08T00:00:00Z
date_updated: 2025-09-30T09:24:17Z
day: '08'
department:
- _id: MiSi
doi: 10.1126/scisignal.2002617
external_id:
isi:
- '000296800500002'
intvolume: ' 4'
isi: 1
issue: '198'
language:
- iso: eng
month: '11'
oa_version: None
publication: Science Signaling
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '7329'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Setting the clock for recirculating lymphocytes
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 4
year: '2011'
...
---
_id: '518'
abstract:
- lang: eng
text: Cancer stem cells or cancer initiating cells are believed to contribute to
cancer recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with
fundamental roles in gene regulation. The role of miRNAs in cancer stem cells
is only poorly understood. Here, we report miRNA expression profiles of glioblastoma
stem cell-containing CD133 + cell populations. We find that miR-9, miR-9 * (referred
to as miR-9/9 *), miR-17 and miR-106b are highly abundant in CD133 + cells. Furthermore,
inhibition of miR-9/9 * or miR-17 leads to reduced neurosphere formation and stimulates
cell differentiation. Calmodulin-binding transcription activator 1 (CAMTA1) is
a putative transcription factor, which induces the expression of the anti-proliferative
cardiac hormone natriuretic peptide A (NPPA). We identify CAMTA1 as an miR-9/9
* and miR-17 target. CAMTA1 expression leads to reduced neurosphere formation
and tumour growth in nude mice, suggesting that CAMTA1 can function as tumour
suppressor. Consistently, CAMTA1 and NPPA expression correlate with patient survival.
Our findings could provide a basis for novel strategies of glioblastoma therapy.
article_processing_charge: No
article_type: original
author:
- first_name: Daniel
full_name: Schraivogel, Daniel
last_name: Schraivogel
- first_name: Lasse
full_name: Weinmann, Lasse
last_name: Weinmann
- first_name: Dagmar
full_name: Beier, Dagmar
last_name: Beier
- first_name: Ghazaleh
full_name: Tabatabai, Ghazaleh
last_name: Tabatabai
- first_name: Alexander
full_name: Eichner, Alexander
id: 4DFA52AE-F248-11E8-B48F-1D18A9856A87
last_name: Eichner
- first_name: Jia
full_name: Zhu, Jia
last_name: Zhu
- first_name: Martina
full_name: Anton, Martina
last_name: Anton
- 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: Michael
full_name: Weller, Michael
last_name: Weller
- first_name: Christoph
full_name: Beier, Christoph
last_name: Beier
- first_name: Gunter
full_name: Meister, Gunter
last_name: Meister
citation:
ama: Schraivogel D, Weinmann L, Beier D, et al. CAMTA1 is a novel tumour suppressor
regulated by miR-9/9 * in glioblastoma stem cells. EMBO Journal. 2011;30(20):4309-4322.
doi:10.1038/emboj.2011.301
apa: Schraivogel, D., Weinmann, L., Beier, D., Tabatabai, G., Eichner, A., Zhu,
J., … Meister, G. (2011). CAMTA1 is a novel tumour suppressor regulated by miR-9/9
* in glioblastoma stem cells. EMBO Journal. Wiley-Blackwell. https://doi.org/10.1038/emboj.2011.301
chicago: Schraivogel, Daniel, Lasse Weinmann, Dagmar Beier, Ghazaleh Tabatabai,
Alexander Eichner, Jia Zhu, Martina Anton, et al. “CAMTA1 Is a Novel Tumour Suppressor
Regulated by MiR-9/9 * in Glioblastoma Stem Cells.” EMBO Journal. Wiley-Blackwell,
2011. https://doi.org/10.1038/emboj.2011.301.
ieee: D. Schraivogel et al., “CAMTA1 is a novel tumour suppressor regulated
by miR-9/9 * in glioblastoma stem cells,” EMBO Journal, vol. 30, no. 20.
Wiley-Blackwell, pp. 4309–4322, 2011.
ista: Schraivogel D, Weinmann L, Beier D, Tabatabai G, Eichner A, Zhu J, Anton M,
Sixt MK, Weller M, Beier C, Meister G. 2011. CAMTA1 is a novel tumour suppressor
regulated by miR-9/9 * in glioblastoma stem cells. EMBO Journal. 30(20), 4309–4322.
mla: Schraivogel, Daniel, et al. “CAMTA1 Is a Novel Tumour Suppressor Regulated
by MiR-9/9 * in Glioblastoma Stem Cells.” EMBO Journal, vol. 30, no. 20,
Wiley-Blackwell, 2011, pp. 4309–22, doi:10.1038/emboj.2011.301.
short: D. Schraivogel, L. Weinmann, D. Beier, G. Tabatabai, A. Eichner, J. Zhu,
M. Anton, M.K. Sixt, M. Weller, C. Beier, G. Meister, EMBO Journal 30 (2011) 4309–4322.
date_created: 2018-12-11T11:46:55Z
date_published: 2011-10-19T00:00:00Z
date_updated: 2025-09-30T09:23:51Z
day: '19'
department:
- _id: MiSi
doi: 10.1038/emboj.2011.301
external_id:
isi:
- '000296715800018'
pmid:
- '21857646'
intvolume: ' 30'
isi: 1
issue: '20'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199389/
month: '10'
oa: 1
oa_version: Submitted Version
page: 4309 - 4322
pmid: 1
publication: EMBO Journal
publication_status: published
publisher: Wiley-Blackwell
publist_id: '7301'
quality_controlled: '1'
scopus_import: '1'
status: public
title: CAMTA1 is a novel tumour suppressor regulated by miR-9/9 * in glioblastoma
stem cells
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 30
year: '2011'
...
---
_id: '3505'
abstract:
- lang: eng
text: Cell migration on two-dimensional (2D) substrates follows entirely different
rules than cell migration in three-dimensional (3D) environments. This is especially
relevant for leukocytes that are able to migrate in the absence of adhesion receptors
within the confined geometry of artificial 3D extracellular matrix scaffolds and
within the interstitial space in vivo. Here, we describe in detail a simple and
economical protocol to visualize dendritic cell migration in 3D collagen scaffolds
along chemotactic gradients. This method can be adapted to other cell types and
may serve as a physiologically relevant paradigm for the directed locomotion of
most amoeboid cells.
alternative_title:
- Methods in Molecular Biology
article_processing_charge: No
article_type: original
author:
- 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: Tim
full_name: Lämmermann, Tim
last_name: Lämmermann
citation:
ama: Sixt MK, Lämmermann T. In vitro analysis of chemotactic leukocyte migration
in 3D environments. Cell Migration. 2011;769:149-165. doi:10.1007/978-1-61779-207-6_11
apa: Sixt, M. K., & Lämmermann, T. (2011). In vitro analysis of chemotactic
leukocyte migration in 3D environments. Cell Migration. Springer. https://doi.org/10.1007/978-1-61779-207-6_11
chicago: Sixt, Michael K, and Tim Lämmermann. “In Vitro Analysis of Chemotactic
Leukocyte Migration in 3D Environments.” Cell Migration. Springer, 2011.
https://doi.org/10.1007/978-1-61779-207-6_11.
ieee: M. K. Sixt and T. Lämmermann, “In vitro analysis of chemotactic leukocyte
migration in 3D environments,” Cell Migration, vol. 769. Springer, pp.
149–165, 2011.
ista: Sixt MK, Lämmermann T. 2011. In vitro analysis of chemotactic leukocyte migration
in 3D environments. Cell Migration. 769, 149–165.
mla: Sixt, Michael K., and Tim Lämmermann. “In Vitro Analysis of Chemotactic Leukocyte
Migration in 3D Environments.” Cell Migration, vol. 769, Springer, 2011,
pp. 149–65, doi:10.1007/978-1-61779-207-6_11.
short: M.K. Sixt, T. Lämmermann, Cell Migration 769 (2011) 149–165.
corr_author: '1'
date_created: 2018-12-11T12:03:41Z
date_published: 2011-05-17T00:00:00Z
date_updated: 2024-10-21T06:03:02Z
day: '17'
department:
- _id: MiSi
doi: 10.1007/978-1-61779-207-6_11
intvolume: ' 769'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://pure.mpg.de/pubman/item/item_3219628_1/component/file_3219630/Sixt%20et%20al..pdf
month: '05'
oa: 1
oa_version: Published Version
page: 149 - 165
publication: Cell Migration
publication_status: published
publisher: Springer
publist_id: '2882'
quality_controlled: '1'
scopus_import: '1'
status: public
title: In vitro analysis of chemotactic leukocyte migration in 3D environments
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 769
year: '2011'
...
---
OA_place: publisher
_id: '3275'
abstract:
- lang: eng
text: 'Chemokines organize immune cell trafficking by inducing either directed (tactic)
or random (kinetic) migration and by activating integrins in order to support
surface adhesion (haptic). Beyond that the same chemokines can establish clearly
defined functional areas in secondary lymphoid organs. Until now it is unclear
how chemokines can fulfill such diverse functions. One decisive prerequisite to
explain these capacities is to know how chemokines are presented in tissue. In
theory chemokines could occur either soluble or immobilized, and could be distributed
either homogenously or as a concentration gradient. To dissect if and how the
presenting mode of chemokines influences immune cells, I tested the response of
dendritic cells (DCs) to differentially displayed chemokines. DCs are antigen
presenting cells that reside in the periphery and migrate into draining lymph
nodes (LNs) once exposed to inflammatory stimuli to activate naïve T cells. DCs
are guided to and within the LN by the chemokine receptor CCR7, which has two
ligands, the chemokines CCL19 and CCL21. Both CCR7 ligands are expressed by fibroblastic
reticular cells in the LN, but differ in their ability to bind to heparan sulfate
residues. CCL21 has a highly charged C-terminal extension, which mediates binding
to anionic surfaces, whereas CCL19 is lacking such residues and likely distributes
as a soluble molecule. This study shows that surface-bound CCL21 causes random,
haptokinetic DC motility, which is confined to the chemokine coated area by insideout
activation of β2 integrins that mediate cell binding to the surface. CCL19 on
the other hand forms concentration gradients which trigger directional, chemotactic
movement, but no surface adhesion. In addition DCs can actively manipulate this
system by recruiting and activating serine proteases on their surfaces, which
create - by proteolytically removing the adhesive C-terminus - a solubilized variant
of CCL21 that functionally resembles CCL19. By generating a CCL21 concentration
gradient DCs establish a positive feedback loop to recruit further DCs from the
periphery to the CCL21 coated region. In addition DCs can sense chemotactic gradients
as well as immobilized haptokinetic fields at the same time and integrate these
signals. The result is chemotactically biased haptokinesis - directional migration
confined to a chemokine coated track or area - which could explain the dynamic
but spatially tightly controlled swarming leukocyte locomotion patterns that have
been observed in lymphatic organs by intravital microscopists. The finding that
DCs can approach soluble cues in a non-adhesive manner while they attach to surfaces
coated with immobilized cues raises the question how these cells transmit intracellular
forces to the environment, especially in the non-adherent migration mode. In order
to migrate, cells have to generate and transmit force to the extracellular substrate.
Force transmission is the prerequisite to procure an expansion of the leading
edge and a forward motion of the whole cell body. In the current conceptions actin
polymerization at the leading edge is coupled to extracellular ligands via the
integrin family of transmembrane receptors, which allows the transmission of intracellular
force. Against the paradigm of force transmission during migration, leukocytes,
like DCs, are able to migrate in threedimensional environments without using integrin
transmembrane receptors (Lämmermann et al., 2008). This reflects the biological
function of leukocytes, as they can invade almost all tissues, whereby their migration
has to be independent from the extracellular environment. How the cells can achieve
this is unclear. For this study I examined DC migration in a defined threedimensional
environment and highlighted actin-dynamics with the probe Lifeact-GFP. The result
was that chemotactic DCs can switch between integrin-dependent and integrin- independent
locomotion and can thereby adapt to the adhesive properties of their environment.
If the cells are able to couple their actin cytoskeleton to the substrate, actin
polymerization is entirely converted into protrusion. Without coupling the actin
cortex undergoes slippage and retrograde actin flow can be observed. But retrograde
actin flow can be completely compensated by higher actin polymerization rate keeping
the migration velocity and the shape of the cells unaltered. Mesenchymal cells
like fibroblast cannot balance the loss of adhesive interaction, cannot protrude
into open space and, therefore, strictly depend on integrinmediated force coupling.
This leukocyte specific phenomenon of “adaptive force transmission” endows these
cells with the unique ability to transit and invade almost every type of tissue. '
acknowledgement: "I would like to express my sincere gratitude to the following people
who made with their continuous support and encouragement this thesis possible: First,
I want to thank Prof. Dr. Michael Sixt for his excellent supervision and mentoring,
especially for the nice, relaxed working atmosphere, a lot of brilliant ideas and
the freedom to work in my own way.\r\n\r\nProf. Dr. Reinhard Fässler for his constant
support of the Sixt lab and for providing excellent working conditions. \r\n\r\nProf.
Dr. Sanjiv Luther and Prof. Dr. Tobias Bollenbach for agreeing to be member of my
thesis committee and to evaluate my work.\r\n\r\nDr. Walther Göhring, Carmen Schmitz,
the Recombinant Protein Production core facility and the animal care takers for
providing the “infrastructure” for this thesis. \r\n\r\nProf. Dr. Daniel Legler,
Markus Bruckner and Dr. Julien Polleux for very fruitful collaborations and discussions.\r\n\r\nMy
labmates for their help, a lot of discussions and to make the Sixt lab to a convenient
place to work : Karin Hirsch, Tim Lämmeramnn, Holger Pflicke, Jörg Renkawitz, Michele
Weber and Alexander Eichner All members of the Department of Molecular Medicine
for their help. Especially I want to thank Sarah Schmidt, Karin Hirsch and Raphael
Ruppert for their friendship, nice chats and their uncensored point of view. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Kathrin
full_name: Schumann, Kathrin
id: F44D762E-4F9D-11E9-B64C-9EB26CEFFB5F
last_name: Schumann
citation:
ama: Schumann K. The role of chemotactic gradients in dendritic cell migration.
2011.
apa: Schumann, K. (2011). The role of chemotactic gradients in dendritic cell
migration. Institute of Science and Technology Austria.
chicago: Schumann, Kathrin. “The Role of Chemotactic Gradients in Dendritic Cell
Migration.” Institute of Science and Technology Austria, 2011.
ieee: K. Schumann, “The role of chemotactic gradients in dendritic cell migration,”
Institute of Science and Technology Austria, 2011.
ista: Schumann K. 2011. The role of chemotactic gradients in dendritic cell migration.
Institute of Science and Technology Austria.
mla: Schumann, Kathrin. The Role of Chemotactic Gradients in Dendritic Cell Migration.
Institute of Science and Technology Austria, 2011.
short: K. Schumann, The Role of Chemotactic Gradients in Dendritic Cell Migration,
Institute of Science and Technology Austria, 2011.
corr_author: '1'
date_created: 2018-12-11T12:02:24Z
date_published: 2011-03-01T00:00:00Z
date_updated: 2026-04-09T14:36:24Z
day: '01'
ddc:
- '570'
- '579'
degree_awarded: PhD
department:
- _id: MiSi
file:
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checksum: e69eee6252660f0b694a2ea8923ddc72
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date_created: 2019-03-26T08:12:21Z
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file_date_updated: 2021-02-22T11:24:30Z
has_accepted_license: '1'
language:
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month: '03'
oa: 1
oa_version: Published Version
page: '141'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '3371'
pubrep_id: '11'
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
title: The role of chemotactic gradients in dendritic cell migration
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2011'
...