Effects of Cell Tension on the Small GTPase Rac

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, w...

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Bibliographic Details
Published in:The Journal of cell biology 2002-07, Vol.158 (1), p.153-164
Main Authors: Katsumi, Akira, Milanini, Julie, Kiosses, William B., del Pozo, Miguel A., Kaunas, Roland, Chien, Shu, Hahn, Klaus M., Schwartz, Martin Alexander
Format: Article
Language:English
Subjects:
Amides - pharmacology
Animals
Azepines - pharmacology
B lymphocytes
Cell Line
Cell Membrane - metabolism
Cell Movement
Cells
Cellular biology
Collagen - pharmacology
Collagens
Dose-Response Relationship, Drug
Endothelial cells
Energy Transfer
Fibroblasts
GTP Phosphohydrolases - metabolism
Guanine Nucleotide Exchange Factors
Microscopy, Fluorescence
Microscopy, Phase-Contrast
Microscopy, Video
Naphthalenes - pharmacology
Neoplasm Proteins
NIH 3T3 cells
Physiological regulation
Proteins - metabolism
Pseudopodia
Pseudopodia - metabolism
Pyridines - pharmacology
rac GTP-Binding Proteins - metabolism
Rats
Stress fibers
Stress, Mechanical
T lymphocytes
T-Lymphoma Invasion and Metastasis-inducing Protein 1
Time Factors
Transfection
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200201105