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Published 8 July 2002. doi:10.1083/jcb.200201105
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© The Rockefeller University Press, 0021-9525/2002/7/153 $5.00
The Journal of Cell Biology, Volume 158, Number 1, July 8, 2002 153-164

Article

Effects of cell tension on the small GTPase Rac



Akira Katsumi1, Julie Milanini1, William B. Kiosses1, Miguel A. del Pozo1, Roland Kaunas3, Shu Chien3, Klaus M. Hahn2 and Martin Alexander Schwartz1

1 Division of Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037
2 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037
3 Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California San Diego, CA 92093

Address correspondence to M.A. Schwartz, Department of Vascular Biology, CVN228/VB4, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037. Tel.: (858) 784-7140. Fax: (858) 784-7360. E-mail: schwartz{at}scripps.edu

Cells in the body are subjected to mechanical stresses such as tension, compression, and shear stress. These mechanical stresses play important roles in both physiological and pathological processes; however, mechanisms transducing mechanical stresses into biochemical signals remain elusive. Here, we demonstrated that equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac. Nearly maximal effects on Rac activity were obtained with 10% strain. GAP-resistant, constitutively active V12Rac reversed this inhibition, supporting a critical role for Rac inhibition in the response to stretch. In contrast, activation of endogenous Rac with a constitutively active nucleotide exchange factor did not, suggesting that regulation of GAP activity most likely mediates the inhibition. Uniaxial stretch suppressed lamellipodia along the sides lengthened by stretch and increased it at the adjacent ends. A fluorescence assay for localized Rac showed comparable changes in activity along the sides versus the ends after uniaxial stretch. Blocking polarization of Rac activity by expressing V12Rac prevented subsequent alignment of actin stress fibers. Treatment with Y-27632 or ML-7 that inhibits myosin phosphorylation and contractility increased lamellipodia through Rac activation and decreased cell polarization. We hypothesize that regulation of Rac activity by tension may be important for motility, polarization, and directionality of cell movement.

Key Words: mechanotransduction; mechanical stretch; lamellipodia; polarization; Rac


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