title: Changes in cholesterol levels in the plasma membrane modulate cell signaling and regulate cell adhesion and migration on fibronectin.
abstract: The number and distribution of lipid molecules, including cholesterol in particular, in the plasma membrane, may play a key role in regulating several physiological processes in cells. We investigated the role of membrane cholesterol in regulating cell shape, adhesion and motility. The acute depletion of cholesterol from the plasma membrane of cells that were well spread and motile on fibronectin caused the rounding of these cells and decreased their adhesion to and motility on fibronectin. These modifications were less pronounced in cells plated on laminin, vitronectin or plastic, indicating that cholesterol-mediated changes in adhesion and motility are more specific for adhesion mediated by fibronectin-specific integrins, such as alpha5beta1. These changes were accompanied by remodeling of the actin cytoskeleton, the spatial reorganization of paxillin in the membrane, and changes to the dynamics of alpha5 integrin and paxillin-rich focal adhesions. Levels of tyrosine phosphorylation at position 576/577 of FAK and Erk1/Erk2 MAP-kinase activity levels were both lower in cholesterol-depleted than in control cells. These levels normalized only on fibronectin when cholesterol was reincorporated into the cell membrane. Thus, membrane cholesterol content has a specific effect on certain signaling pathways specifically involved in regulating cell motility on fibronectin and organization of the actin cytoskeleton.
authors.affiliation: Center for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: O G
authors.initials: OG
authors.lastname: Ramprasad
authors.forename: G
authors.initials: G
authors.lastname: Srinivas
authors.forename: K Sridhar
authors.initials: KS
authors.lastname: Rao
authors.forename: Powrnima
authors.initials: P
authors.lastname: Joshi
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dufour
authors.forename: Gopal
authors.initials: G
authors.lastname: Pande
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism*; D002465:Cell Movement; D002784:Cholesterol / Q000172:deficiency / Q000378:metabolism*; D003599:Cytoskeleton / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D000199:Actins; D005353:Fibronectins; D039081:Integrin alpha5beta1; D051419:Paxillin; D002784:Cholesterol; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases