Molecular mechanism for orienting membrane and actin dynamics to nascent cell-cell contacts in epithelial cells.
The small GTPase Rac1 has been implicated in regulation of cell migration and cell-cell adhesion in epithelial cells. Little is known, however, about the spatial and temporal coordination of Rac1 activity required to balance these competing processes. We fractionated endogenous Rac1-containing protein complexes from membranes of Madin-Darby canine kidney cells and identified three major complexes comprising a Rac1.PAK (p21-activated kinase) complex, and 11 S and 16 S Rac1 complexes. Significantly, Rac1 shifts from the 11 S to a 16 S particle during initiation of cell-cell adhesion. This shift may reflect a diffusion trapping mechanism by which these Rac1 complexes are localized to cadherin-mediated cell-cell contacts through an interaction with annexin II.
Hansen
Marc D H
MD
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305-5426, USA.
Ehrlich
Jason S
JS
Nelson
W James
WJ
D000199:Actins / Q000378:metabolism*; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism; D017306:Annexin A2 / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002867:Chromones / Q000378:metabolism; D004285:Dogs; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism*; D046911:Macromolecular Substances; D009025:Morpholines / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D017305:Annexin A1; D017306:Annexin A2; D015820:Cadherins; D002867:Chromones; D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020830:rac1 GTP-Binding Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one