O'Brien L E, Jou T S, Pollack A L, Zhang Q, Hansen S H, Yurchenco P, Mostov K E
Department of Anatomy, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Nat Cell Biol. 2001 Sep;3(9):831-8. doi: 10.1038/ncb0901-831.
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.
细胞极化涉及沿细胞内轴产生不对称性。在多细胞组织中，单个细胞的不对称性必须与组织的上层结构相适应。然而，将细胞极化与组织形态发生联系起来的机制仍知之甚少。在这里，我们报告在发育中的Madin-Darby犬肾（MDCK）上皮囊肿中，顶端极性的定向需要小GTP酶Rac1和基底膜成分层粘连蛋白。显性负性Rac1改变了内源性MDCK层粘连蛋白的超分子组装，并导致顶端极性的显著反转。外源性层粘连蛋白被募集到这些囊肿的表面并挽救顶端极性。这些发现表明Rac1介导的层粘连蛋白组装参与顶端极定向。通过将顶端定向与基底膜的生成联系起来，上皮细胞确保了极性与组织结构的协调。
