Coordination of Rho GTPase activities during cell protrusion

Matthias MacHacek, Louis Hodgson, Christopher Welch, Hunter Elliott, Olivier Pertz, Perihan Nalbant, Amy Abell, Gary L. Johnson, Klaus M. Hahn, Gaudenz Danuser

Research output: Contribution to journalArticle

602 Scopus citations

Abstract

The GTPases Rac1, RhoA and Cdc42 act together to control cytoskeleton dynamics. Recent biosensor studies have shown that all three GTPases are activated at the front of migrating cells, and biochemical evidence suggests that they may regulate one another: Cdc42 can activate Rac1 (ref. 8), and Rac1 and RhoA are mutually inhibitory. However, their spatiotemporal coordination, at the seconds and single-micrometre dimensions typical of individual protrusion events, remains unknown. Here we examine GTPase coordination in mouse embryonic fibroblasts both through simultaneous visualization of two GTPase biosensors and using a ĝ€? computational multiplexingĝ€™ approach capable of defining the relationships between multiple protein activities visualized in separate experiments. We found that RhoA is activated at the cell edge synchronous with edge advancement, whereas Cdc42 and Rac1 are activated 2 m behind the edge with a delay of 40 s. This indicates that Rac1 and RhoA operate antagonistically through spatial separation and precise timing, and that RhoA has a role in the initial events of protrusion, whereas Rac1 and Cdc42 activate pathways implicated in reinforcement and stabilization of newly expanded protrusions.

Original languageEnglish (US)
Pages (from-to)99-103
Number of pages5
JournalNature
Volume461
Issue number7260
DOIs
StatePublished - Sep 3 2009

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Coordination of Rho GTPase activities during cell protrusion'. Together they form a unique fingerprint.

  • Cite this

    MacHacek, M., Hodgson, L., Welch, C., Elliott, H., Pertz, O., Nalbant, P., Abell, A., Johnson, G. L., Hahn, K. M., & Danuser, G. (2009). Coordination of Rho GTPase activities during cell protrusion. Nature, 461(7260), 99-103. https://doi.org/10.1038/nature08242