Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly.
Cellular polarization involves the generation of asymmetry along an intracellular axis. In a multicellular tissue, the asymmetry of individual cells must conform to the overlying architecture of the tissue. However, the mechanisms that couple cellular polarization to tissue morphogenesis are poorly understood. Here, we report that orientation of apical polarity in developing Madin-Darby canine kidney (MDCK) epithelial cysts requires the small GTPase Rac1 and the basement membrane component laminin. Dominant-negative Rac1 alters the supramolecular assembly of endogenous MDCK laminin and causes a striking inversion of apical polarity. Exogenous laminin is recruited to the surface of these cysts and rescues apical polarity. These findings implicate Rac1-mediated laminin assembly in apical pole orientation. By linking apical orientation to generation of the basement membrane, epithelial cells ensure the coordination of polarity with tissue architecture.
O'Brien
L E
LE
Department of Anatomy, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Jou
T S
TS
Pollack
A L
AL
Zhang
Q
Q
Hansen
S H
SH
Yurchenco
P
P
Mostov
K E
KE
D000199:Actins / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure; D016764:Cell Polarity / Q000502:physiology*; D003094:Collagen; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D007668:Kidney; D007797:Laminin / Q000032:analysis / Q000378:metabolism*; D008954:Models, Biological; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D007797:Laminin; D011994:Recombinant Proteins; D003094:Collagen; D020830:rac1 GTP-Binding Protein