Cholesterol-regulated stress fiber formation.
Dynamic interactions between cellular membranes and the cytoskeleton are known to play major roles in many cellular responses to environmental cues. External signals resulting in proliferation, differentiation, polarization, and motility must be translated from chemical signals into changes of state, often involving the cytoskeleton-dependent altering of cell shape and redistribution of molecules. Cholesterol, a critical component of eukaryotic cell membranes, performs vital roles in regulating membrane dynamics and function. Here we demonstrate, using mesenchymal and epithelial cell lines, that depletion of membrane cholesterol results in Src kinase-mediated Rho activation and caveolin phosphorylation, which together collaborate to form stress fibers. These results demonstrate that cholesterol is a critical regulator of membrane-cytoskeletal dynamics and suggest that altered cholesterol concentrations may result in dramatic changes in cellular responses mediated by the cytoskeleton.
Qi
Maosong
M
Department of Orthopaedic Surgery, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Liu
Yuzhen
Y
Freeman
Michael R
MR
Solomon
Keith R
KR
D016475:3T3 Cells; D000818:Animals; D022461:Caveolins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D015398:Signal Transduction / Q000502:physiology; D022502:Stress Fibers / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D022461:Caveolins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020742:rhoA GTP-Binding Protein