title: Integrins regulate Rac targeting by internalization of membrane domains.
abstract: Translocation of the small GTP-binding protein Rac1 to the cell plasma membrane is essential for activating downstream effectors and requires integrin-mediated adhesion of cells to extracellular matrix. We report that active Rac1 binds preferentially to low-density, cholesterol-rich membranes, and specificity is determined at least in part by membrane lipids. Cell detachment triggered internalization of plasma membrane cholesterol and lipid raft markers. Preventing internalization maintained Rac1 membrane targeting and effector activation in nonadherent cells. Regulation of lipid rafts by integrin signals may regulate the location of membrane domains such as lipid rafts and thereby control domain-specific signaling events in anchorage-dependent cells.
authors.affiliation: Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. mdelpozo@scripps.edu
authors.forename: Miguel A
authors.initials: MA
authors.lastname: del Pozo
authors.forename: Nazilla B
authors.initials: NB
authors.lastname: Alderson
authors.forename: William B
authors.initials: WB
authors.lastname: Kiosses
authors.forename: Hui-Hsien
authors.initials: HH
authors.lastname: Chiang
authors.forename: Richard G W
authors.initials: RG
authors.lastname: Anderson
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D017261:Glycosylphosphatidylinositols; D019012:Integrin beta1; D016023:Integrins; D008081:Liposomes; D011993:Recombinant Fusion Proteins; D005677:G(M1) Ganglioside; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D002784:Cholesterol; D020830:rac1 GTP-Binding Protein