Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila

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 Biol. 20(1), e3001494.

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Journal Article | Published | English
Abstract
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.
Publishing Year
Date Published
2022-01-06
Journal Title
PLoS Biol
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.
Acknowledged SSUs
Volume
20
Issue
1
Page
e3001494
ISSN
eISSN
IST-REx-ID

Cite this

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 Biol. 2022;20(1):e3001494. doi:10.1371/journal.pbio.3001494
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 Biol. Public Library of Science. https://doi.org/10.1371/journal.pbio.3001494
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 Biol. Public Library of Science, 2022. https://doi.org/10.1371/journal.pbio.3001494.
V. Belyaeva et al., “Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila,” PLoS Biol, vol. 20, no. 1. Public Library of Science, p. e3001494, 2022.
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 Biol. 20(1), e3001494.
Belyaeva, Vera, et al. “Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” PLoS Biol, vol. 20, no. 1, Public Library of Science, 2022, p. e3001494, doi:10.1371/journal.pbio.3001494.
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