Rho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cyclesShow others and affiliations
2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 8356Article in journal (Refereed) Published
Abstract [en]
Rho GTPases play a key role in the spatio-temporal coordination of cytoskeletal dynamics during cell migration. Here, we directly investigate crosstalk between the major Rho GTPases Rho, Rac and Cdc42 by combining rapid activity perturbation with activity measurements in mammalian cells. These studies reveal that Rac stimulates Rho activity. Direct measurement of spatio-temporal activity patterns show that Rac activity is tightly and precisely coupled to local cell protrusions, followed by Rho activation during retraction. Furthermore, we find that the Rho-activating Lbc-type GEFs Arhgef11 and Arhgef12 are enriched at transient cell protrusions and retractions and recruited to the plasma membrane by active Rac. In addition, their depletion reduces activity crosstalk, cell protrusion-retraction dynamics and migration distance and increases migration directionality. Thus, our study shows that Arhgef11 and Arhgef12 facilitate exploratory cell migration by coordinating cell protrusion and retraction by coupling the activity of the associated regulators Rac and Rho.
Place, publisher, year, edition, pages
Springer Nature, 2023. Vol. 14, no 1, article id 8356
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:umu:diva-218688DOI: 10.1038/s41467-023-43875-yISI: 001126102000016PubMedID: 38102112Scopus ID: 2-s2.0-85179734469OAI: oai:DiVA.org:umu-218688DiVA, id: diva2:1822757
Funder
German Research Foundation (DFG), 823/3-1, 823/9-1, 823/4-1, 823/6-1, 823/8-1, 823/10-1Knut and Alice Wallenberg FoundationGöran Gustafsson Foundation for Research in Natural Sciences and MedicineSwedish Research Council, 2018-045852023-12-272023-12-272025-04-24Bibliographically approved