Laminin 511 partners with laminin 332 to mediate directional migration of Madin–Darby canine kidney epithelial cells

作者：Patricia G. Greciano, José V. Moyano, Mary M. Buschmann, Jun Tang, Yue Lü, Jean Rudnicki, Aki Manninen, Karl S. Matlin · 发表于：Molecular Biology of the Cell · 年份：2011 · DOI：10.1091/mbc.e11-08-0718 · 被引用次数：19 · 研究领域：Cell Adhesion Molecules Research、Cellular Mechanics and Interactions、Wnt/β-catenin signaling in development and cancer

Sustained directional migration of epithelial cells is essential for regeneration of injured epithelia. Front-rear polarity of migrating cells is determined by local activation of a signaling network involving Cdc42 and other factors in response to spatial cues from the environment, the nature of which are obscure. We examined the roles of laminin (LM)-511 and LM-332, two structurally different laminin isoforms, in the migration of Madin-Darby canine kidney cells by suppressing expression of their α subunits using RNA interference. We determined that knockdown of LM-511 inhibits directional migration and destabilizes cell-cell contacts, in part by disturbing the localization and activity of the polarization machinery. Suppression of integrin α3, a laminin receptor subunit, in cells synthesizing normal amounts of both laminins has a similar effect as knockdown of LM-511. Surprisingly, simultaneous suppression of both laminin α5 and laminin α3 restores directional migration and cell-cell contact stability, suggesting that cells recognize a haptotactic gradient formed by a combination of laminins.