Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila.
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 bee...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
|
| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001494&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850027684133863424 |
|---|---|
| author | Vera Belyaeva Stephanie Wachner Attila Gyoergy Shamsi Emtenani Igor Gridchyn Maria Akhmanova Markus Linder Marko Roblek Maria Sibilia Daria Siekhaus |
| author_facet | Vera Belyaeva Stephanie Wachner Attila Gyoergy Shamsi Emtenani Igor Gridchyn Maria Akhmanova Markus Linder Marko Roblek Maria Sibilia Daria Siekhaus |
| author_sort | Vera Belyaeva |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d00742cb5c804860a3e34bce11e7bde5 |
| institution | DOAJ |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-d00742cb5c804860a3e34bce11e7bde52025-08-20T03:00:05ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-01-01201e300149410.1371/journal.pbio.3001494Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila.Vera BelyaevaStephanie WachnerAttila GyoergyShamsi EmtenaniIgor GridchynMaria AkhmanovaMarkus LinderMarko RoblekMaria SibiliaDaria SiekhausThe 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.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001494&type=printable |
| spellingShingle | Vera Belyaeva Stephanie Wachner Attila Gyoergy Shamsi Emtenani Igor Gridchyn Maria Akhmanova Markus Linder Marko Roblek Maria Sibilia Daria Siekhaus Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. PLoS Biology |
| title | Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. |
| title_full | Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. |
| title_fullStr | Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. |
| title_full_unstemmed | Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. |
| title_short | Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. |
| title_sort | fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin based mechanism in drosophila |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001494&type=printable |
| work_keys_str_mv | AT verabelyaeva fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila AT stephaniewachner fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila AT attilagyoergy fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila AT shamsiemtenani fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila AT igorgridchyn fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila AT mariaakhmanova fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila AT markuslinder fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila AT markoroblek fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila AT mariasibilia fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila AT dariasiekhaus fosregulatesmacrophageinfiltrationagainstsurroundingtissueresistancebyacorticalactinbasedmechanismindrosophila |