RGD Reference Report - Effects of cell tension on the small GTPase Rac. - Rat Genome Database

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Effects of cell tension on the small GTPase Rac.

Authors: Katsumi, A  Milanini, J  Kiosses, WB  Del Pozo, MA  Kaunas, R  Chien, S  Hahn, KM  Schwartz, MA 
Citation: Katsumi A, etal., J Cell Biol 2002 Jul 8;158(1):153-64. Epub 2002 Jul 8.
RGD ID: 1299247
Pubmed: (View Article at PubMed) PMID:12105187
DOI: Full-text: DOI:10.1083/jcb.200201105

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.

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Rac1  (Rac family small GTPase 1)

Additional Information