Rac1 activity is required for cardiac myocyte alignment in response to mechanical stress.
Mechanical stretch is essential for the cardiac growth. The exposure of cardiac myocytes to the mechanical stretch leads to the cell alignment in parallel to the stretch direction, determining the cell polarity, though it remains to be addressed how mechanical stretch regulates cell orientation. In the present study, we investigated the signal transduction pathways responsible for the cell orientation response to mechanical stretch, focusing on Rho family proteins. Neonatal rat cardiomyocytes were cultured on silicon chambers and exposed to artificial uniaxial cyclic stretch. The pull-down assays revealed that Rac1 was rapidly activated by stretch, but not RhoA. To analyze the roles of Rho family proteins in cardiomyocyte orientation, adenoviral vectors expressing dominant-negative (dn) RhoA and Rac1 were generated. The transfection with adenovirus vector expressing dnRac1, but not dnRhoA, inhibited stretch-induced cell alignment. In conclusion, Rac1 activity is necessary for cardiomyocyte alignment in response to directional stretch.
Yamane
Masako
M
Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita City, Osaka 565-0871, Japan.
Matsuda
Takahisa
T
Ito
Takashi
T
Fujio
Yasushi
Y
Takahashi
Kyoko
K
Azuma
Junichi
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D016764:Cell Polarity / Q000502:physiology; D048430:Cell Shape / Q000502:physiology*; D002478:Cells, Cultured; D005822:Genetic Vectors / Q000235:genetics; D008856:Microscopy, Fluorescence; D009154:Mutation; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D051381:Rats; D011921:Rats, Inbred WKY; D013314:Stress, Mechanical; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein