Rho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles

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dc.contributor.authorNanda, Suchet
dc.contributor.authorCalderon, Abram
dc.contributor.authorSachan, Arya
dc.contributor.authorDuong, Thanh-Thuy
dc.contributor.authorKoch, Johannes
dc.contributor.authorXin, Xiaoyi
dc.contributor.authorSolouk-Stahlberg, Djamschid
dc.contributor.authorWu, Yao-Wen
dc.contributor.authorNalbant, Perihan
dc.contributor.authorDehmelt, Leif
dc.date.accessioned2024-04-05T09:01:35Z
dc.date.available2024-04-05T09:01:35Z
dc.date.issued2023-12-15
dc.description.abstractRho 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.en
dc.identifier.urihttp://hdl.handle.net/2003/42424
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-24260
dc.language.isoende
dc.relation.ispartofseriesNature communications;14
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/de
dc.subjectActinen
dc.subjectLamellipodiaen
dc.subjectRHO signallingen
dc.subject.ddc570
dc.subject.ddc540
dc.titleRho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cyclesen
dc.typeTextde
dc.type.publicationtypeArticlede
dcterms.accessRightsopen access
eldorado.secondarypublicationtruede
eldorado.secondarypublication.primarycitationNanda, S., Calderon, A., Sachan, A. et al. Rho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles. Nat Commun 14, 8356 (2023). https://doi.org/10.1038/s41467-023-43875-yde
eldorado.secondarypublication.primaryidentifierhttps://doi.org/10.1038/s41467-023-43875-yde

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