RT Journal Article SR Electronic T1 Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.09.18.301481 DO 10.1101/2020.09.18.301481 A1 Vera Belyaeva A1 Stephanie Wachner A1 Attila Gyoergy A1 Shamsi Emtenani A1 Igor Gridchyn A1 Maria Akhmanova A1 Markus Linder A1 Marko Roblek A1 Maria Sibilia A1 Daria Siekhaus YR 2021 UL http://biorxiv.org/content/early/2021/09/28/2020.09.18.301481.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.