@article{41529184ce2a43f69727a4841b2b3f3c,
title = "Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly",
abstract = "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.",
author = "O'Brien, {Lucy Erin} and Jou, {Tzuu Shuh} and Pollack, {Anne L.} and Qihang Zhang and Hansen, {Steen H.} and Peter Yurchenco and Mostov, {Keith E.}",
note = "Funding Information: ACKNOWLEDGEMENTS We thank Sandra Huling and the UCSF Liver Center Core Facility for preparing electron micrographs; Peter Bacchetti for biostatistical support; Joshua Thaler for invaluable discussions and advice; Mirjam Zegers, W. James Nelson, Fay Shamanski, Erin Gensch, Henry Bourne, Cori Bargmann, Yuh-Nung Jan, Zena Werb and Daniel Kalman for a critical reading of the manuscript; and Karl Matlin for stimulating discussions. L.E.O. is the recipient of a National Defense Science and Engineering Graduate Fellowship and of a predoctoral fellowship from the American Heart Association. T.S.J. is supported by the National Science Council. S.H.H. is the recipient of an award from the Weimann Foundation. A.L.P. is supported by a NIH training grant postdoctoral fellowship. P.Y. is supported by a grant from the NIH. This investigation was supported by a DAMD grant and NIH grants to K.E.M. Correspondence and requests for materials should be addressed to K.E.M.",
year = "2001",
doi = "10.1038/ncb0901-831",
language = "English (US)",
volume = "3",
pages = "831--838",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Research",
number = "9",
}