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

Suchet Nanda, Abram Calderon, Arya Sachan, Thanh-Thuy Duong, Johannes Koch, Xiaoyi Xin, Djamschid Solouk-Stahlberg, Yao-Wen Wu, Perihan Nalbant () and Leif Dehmelt ()
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Suchet Nanda: TU Dortmund University
Abram Calderon: TU Dortmund University
Arya Sachan: TU Dortmund University
Thanh-Thuy Duong: TU Dortmund University
Johannes Koch: Center of Medical Biotechnology, University of Duisburg-Essen
Xiaoyi Xin: Umeå Centre for Microbial Research, Umeå University
Djamschid Solouk-Stahlberg: TU Dortmund University
Yao-Wen Wu: Umeå Centre for Microbial Research, Umeå University
Perihan Nalbant: Center of Medical Biotechnology, University of Duisburg-Essen
Leif Dehmelt: TU Dortmund University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-43875-y

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