Pak1 regulates focal adhesion strength, myosin IIA distribution, and actin dynamics to optimize cell migration

Violaine D. Delorme-Walker, Jeffrey R. Peterson, Jonathan Chernoff, Clare M. Waterman, Gaudenz Danuser, Céline DerMardirossian, Gary M. Bokoch

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Cell motility requires the spatial and temporal coordination of forces in the actomyosin cytoskeleton with extracellular adhesion. The biochemical mechanism that coordinates filamentous actin (F-actin) assembly, myosin contractility, adhesion dynamics, and motility to maintain the balance between adhesion and contraction remains unknown. In this paper, we show that p21-activated kinases (Paks), downstream effectors of the small guanosine triphosphatases Rac and Cdc42, biochemically couple leading-edge actin dynamics to focal adhesion (FA) dynamics. Quantitative live cell microscopy assays revealed that the inhibition of Paks abolished F-actin flow in the lamella, displaced myosin IIA from the cell edge, and decreased FA turnover. We show that, by controlling the dynamics of these three systems, Paks regulate the protrusive activity and migration of epithelial cells. Furthermore, we found that expressing Pak1 was sufficient to overcome the inhibitory effects of excess adhesion strength on cell motility. These findings establish Paks as critical molecules coordinating cytoskeletal systems for efficient cell migration.

Original languageEnglish (US)
Pages (from-to)1289-1303
Number of pages15
JournalJournal of Cell Biology
Volume193
Issue number7
DOIs
StatePublished - Jun 27 2011

ASJC Scopus subject areas

  • Cell Biology

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    Delorme-Walker, V. D., Peterson, J. R., Chernoff, J., Waterman, C. M., Danuser, G., DerMardirossian, C., & Bokoch, G. M. (2011). Pak1 regulates focal adhesion strength, myosin IIA distribution, and actin dynamics to optimize cell migration. Journal of Cell Biology, 193(7), 1289-1303. https://doi.org/10.1083/jcb.201010059