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Delorme-Walker VD , Peterson JR , Chernoff J , Waterman CM , Danuser G , DerMardirossian C , Bokoch GM
Pak1 regulates focal adhesion strength, myosin IIA distribution, and actin dynamics to optimize cell migration
J Cell Biol. 2011 Jun 27;193(7) :1289-303
PMID: 21708980 PMCID: PMC3216326 URL: https://www.ncbi.nlm.nih.gov/pubmed/21708980
AbstractCell 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.
NotesDelorme-Walker, Violaine D Peterson, Jeffrey R Chernoff, Jonathan Waterman, Clare M Danuser, Gaudenz DerMardirossian, Celine Bokoch, Gary M eng R01 CA117884/CA/NCI NIH HHS/ GM44428/GM/NIGMS NIH HHS/ GM071868/GM/NIGMS NIH HHS/ R01 GM071868-05/GM/NIGMS NIH HHS/ R01 GM039434/GM/NIGMS NIH HHS/ GM39434/GM/NIGMS NIH HHS/ R01 GM071868/GM/NIGMS NIH HHS/ R01 GM044428/GM/NIGMS NIH HHS/ CA117884/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. J Cell Biol. 2011 Jun 27;193(7):1289-303. doi: 10.1083/jcb.201010059.