A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions.
De novo formation of epithelial cell-cell contacts relies on actin-based protrusions as well as tightly controlled turnover of junctional actin once cells encounter each other and adhesion complexes assemble. The specific contributions of individual actin regulators on either protrusion formation or...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5868805?pdf=render |
| _version_ | 1828915363549544448 |
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| author | Hanna Grobe Andrea Wüstenhagen Christian Baarlink Robert Grosse Katharina Grikscheit |
| author_facet | Hanna Grobe Andrea Wüstenhagen Christian Baarlink Robert Grosse Katharina Grikscheit |
| author_sort | Hanna Grobe |
| collection | DOAJ |
| description | De novo formation of epithelial cell-cell contacts relies on actin-based protrusions as well as tightly controlled turnover of junctional actin once cells encounter each other and adhesion complexes assemble. The specific contributions of individual actin regulators on either protrusion formation or junctional actin turnover remain largely unexplored. Based on our previous findings of Formin-like 2 (FMNL2)-mediated control of junctional actin dynamics, we investigated its potential role in membrane protrusions and impact on newly forming epithelial contacts. CRISPR/Cas9-mediated loss of FMNL2 in human MCF10A cells combined with optogenetic control of Rac1 activity confirmed its critical function in the establishment of intercellular contacts. While lamellipodial protrusion rates remained unaffected, FMNL2 knockout cells were characterized by impaired filopodia formation similar to depletion of the Rho GTPase Cdc42. Silencing of Cdc42, however, failed to affect FMNL2-mediated contact formation. Hence, we propose a cell-cell contact-specific and Rac1-mediated function of FMNL2 entirely independent of Cdc42. Consistent with this, direct visualizations of native epithelial junction formation revealed a striking and specifically Rac1- and not Cdc42-dependent recruitment of FMNL2 to newly forming junctions as well as established cell-cell contacts within epithelial sheets. |
| first_indexed | 2024-12-13T20:12:14Z |
| format | Article |
| id | doaj.art-837d6e6cf55c4db3a083e76596c80c44 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T20:12:14Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-837d6e6cf55c4db3a083e76596c80c442022-12-21T23:32:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019471610.1371/journal.pone.0194716A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions.Hanna GrobeAndrea WüstenhagenChristian BaarlinkRobert GrosseKatharina GrikscheitDe novo formation of epithelial cell-cell contacts relies on actin-based protrusions as well as tightly controlled turnover of junctional actin once cells encounter each other and adhesion complexes assemble. The specific contributions of individual actin regulators on either protrusion formation or junctional actin turnover remain largely unexplored. Based on our previous findings of Formin-like 2 (FMNL2)-mediated control of junctional actin dynamics, we investigated its potential role in membrane protrusions and impact on newly forming epithelial contacts. CRISPR/Cas9-mediated loss of FMNL2 in human MCF10A cells combined with optogenetic control of Rac1 activity confirmed its critical function in the establishment of intercellular contacts. While lamellipodial protrusion rates remained unaffected, FMNL2 knockout cells were characterized by impaired filopodia formation similar to depletion of the Rho GTPase Cdc42. Silencing of Cdc42, however, failed to affect FMNL2-mediated contact formation. Hence, we propose a cell-cell contact-specific and Rac1-mediated function of FMNL2 entirely independent of Cdc42. Consistent with this, direct visualizations of native epithelial junction formation revealed a striking and specifically Rac1- and not Cdc42-dependent recruitment of FMNL2 to newly forming junctions as well as established cell-cell contacts within epithelial sheets.http://europepmc.org/articles/PMC5868805?pdf=render |
| spellingShingle | Hanna Grobe Andrea Wüstenhagen Christian Baarlink Robert Grosse Katharina Grikscheit A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions. PLoS ONE |
| title | A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions. |
| title_full | A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions. |
| title_fullStr | A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions. |
| title_full_unstemmed | A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions. |
| title_short | A Rac1-FMNL2 signaling module affects cell-cell contact formation independent of Cdc42 and membrane protrusions. |
| title_sort | rac1 fmnl2 signaling module affects cell cell contact formation independent of cdc42 and membrane protrusions |
| url | http://europepmc.org/articles/PMC5868805?pdf=render |
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