---
_id: '10614'
abstract:
- lang: eng
text: 'The infiltration of immune cells into tissues underlies the establishment
of tissue-resident macrophages and responses to infections and tumors. Yet the
mechanisms immune cells utilize to negotiate tissue barriers in living organisms
are not well understood, and a role for cortical actin has not been examined.
Here, we find that the tissue invasion of Drosophila macrophages, also known as
plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated
by the Drosophila member of the fos proto oncogene transcription factor family
(Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances
F-actin levels around the entire macrophage surface by increasing mRNA levels
of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking
filamin Cheerio, which are themselves required for invasion. Both the filamin
and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous
and thus the assembly of cortical actin, which is a critical function since expressing
a dominant active form of Diaphanous can rescue the Dfos macrophage invasion defect.
In vivo imaging shows that Dfos enhances the efficiency of the initial phases
of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program
in macrophages counteracts the constraint produced by the tension of surrounding
tissues and buffers the properties of the macrophage nucleus from affecting tissue
entry. We thus identify strengthening the cortical actin cytoskeleton through
Dfos as a key process allowing efficient forward movement of an immune cell into
surrounding tissues. '
acknowledged_ssus:
- _id: LifeSc
acknowledgement: 'We thank the following for their contributions: Plasmids were supplied
by the Drosophila Genomics Resource Center (NIH 2P40OD010949-10A1); fly stocks were
provided by K. Brueckner, B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington
Drosophila Stock Center (NIH P40OD018537) and the Vienna Drosophila Resource Center,
FlyBase for essential genomic information, and the BDGP in situ database for data.
For antibodies, we thank the Developmental Studies Hybridoma Bank, which was created
by the Eunice Kennedy Shriver National Institute of Child Health and Human Development
of the NIH and is maintained at the University of Iowa, as well as J. Zeitlinger
for her generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities
for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria
for technical support and assistance with microscopy and FACS analysis. We thank
C. P. Heisenberg, P. Martin, M. Sixt, and Siekhaus group members for discussions
and T. Hurd, A. Ratheesh, and P. Rangan for comments on the manuscript.'
article_processing_charge: No
article_type: original
author:
- first_name: Vera
full_name: Belyaeva, Vera
id: 47F080FE-F248-11E8-B48F-1D18A9856A87
last_name: Belyaeva
- first_name: Stephanie
full_name: Wachner, Stephanie
id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87
last_name: Wachner
- first_name: Attila
full_name: György, Attila
id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87
last_name: György
orcid: 0000-0002-1819-198X
- first_name: Shamsi
full_name: Emtenani, Shamsi
id: 49D32318-F248-11E8-B48F-1D18A9856A87
last_name: Emtenani
orcid: 0000-0001-6981-6938
- first_name: Igor
full_name: Gridchyn, Igor
id: 4B60654C-F248-11E8-B48F-1D18A9856A87
last_name: Gridchyn
orcid: 0000-0002-1807-1929
- first_name: Maria
full_name: Akhmanova, Maria
id: 3425EC26-F248-11E8-B48F-1D18A9856A87
last_name: Akhmanova
orcid: 0000-0003-1522-3162
- first_name: M
full_name: Linder, M
last_name: Linder
- first_name: Marko
full_name: Roblek, Marko
id: 3047D808-F248-11E8-B48F-1D18A9856A87
last_name: Roblek
orcid: 0000-0001-9588-1389
- first_name: M
full_name: Sibilia, M
last_name: Sibilia
- first_name: Daria E
full_name: Siekhaus, Daria E
id: 3D224B9E-F248-11E8-B48F-1D18A9856A87
last_name: Siekhaus
orcid: 0000-0001-8323-8353
citation:
ama: Belyaeva V, Wachner S, György A, et al. Fos regulates macrophage infiltration
against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila.
PLoS Biology. 2022;20(1):e3001494. doi:10.1371/journal.pbio.3001494
apa: Belyaeva, V., Wachner, S., György, A., Emtenani, S., Gridchyn, I., Akhmanova,
M., … Siekhaus, D. E. (2022). Fos regulates macrophage infiltration against surrounding
tissue resistance by a cortical actin-based mechanism in Drosophila. PLoS Biology.
Public Library of Science. https://doi.org/10.1371/journal.pbio.3001494
chicago: Belyaeva, Vera, Stephanie Wachner, Attila György, Shamsi Emtenani, Igor
Gridchyn, Maria Akhmanova, M Linder, Marko Roblek, M Sibilia, and Daria E Siekhaus.
“Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by
a Cortical Actin-Based Mechanism in Drosophila.” PLoS Biology. Public Library
of Science, 2022. https://doi.org/10.1371/journal.pbio.3001494.
ieee: V. Belyaeva et al., “Fos regulates macrophage infiltration against
surrounding tissue resistance by a cortical actin-based mechanism in Drosophila,”
PLoS Biology, vol. 20, no. 1. Public Library of Science, p. e3001494, 2022.
ista: Belyaeva V, Wachner S, György A, Emtenani S, Gridchyn I, Akhmanova M, Linder
M, Roblek M, Sibilia M, Siekhaus DE. 2022. Fos regulates macrophage infiltration
against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila.
PLoS Biology. 20(1), e3001494.
mla: Belyaeva, Vera, et al. “Fos Regulates Macrophage Infiltration against Surrounding
Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” PLoS
Biology, vol. 20, no. 1, Public Library of Science, 2022, p. e3001494, doi:10.1371/journal.pbio.3001494.
short: V. Belyaeva, S. Wachner, A. György, S. Emtenani, I. Gridchyn, M. Akhmanova,
M. Linder, M. Roblek, M. Sibilia, D.E. Siekhaus, PLoS Biology 20 (2022) e3001494.
corr_author: '1'
date_created: 2022-01-12T10:18:17Z
date_published: 2022-01-06T00:00:00Z
date_updated: 2026-06-08T22:30:36Z
day: '06'
ddc:
- '570'
department:
- _id: DaSi
- _id: JoCs
doi: 10.1371/journal.pbio.3001494
ec_funded: 1
external_id:
isi:
- '000971223700001'
pmid:
- '34990456'
file:
- access_level: open_access
checksum: f454212a5522a7818ba4b2892315c478
content_type: application/pdf
creator: cchlebak
date_created: 2022-01-12T13:50:04Z
date_updated: 2022-01-12T13:50:04Z
file_id: '10615'
file_name: 2022_PLOSBio_Belyaeva.pdf
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relation: main_file
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file_date_updated: 2022-01-12T13:50:04Z
has_accepted_license: '1'
intvolume: ' 20'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: e3001494
pmid: 1
project:
- _id: 253B6E48-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29638
name: The role of Drosophila TNF alpha in immune cell invasion
- _id: 26199CA4-B435-11E9-9278-68D0E5697425
grant_number: '24800'
name: Implications of a TGFβ/Dpp-activated subpopulation for Drosophila macrophage
migration
- _id: 2536F660-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '334077'
name: Investigating the role of transporters in invasive migration through junctions
publication: PLoS Biology
publication_identifier:
eissn:
- 1545-7885
issn:
- 1544-9173
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
link:
- relation: earlier_version
url: https://www.biorxiv.org/content/10.1101/2020.09.18.301481
- description: News on the ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/resisting-the-pressure/
record:
- id: '8557'
relation: earlier_version
status: public
- id: '11193'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Fos regulates macrophage infiltration against surrounding tissue resistance
by a cortical actin-based mechanism in Drosophila
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: 20
year: '2022'
...