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

• Published in: Molecular biology of the cell 2012-01, Vol.23 (1), p.121-136
• Main Authors: Greciano, Patricia G, Moyano, Jose V, Buschmann, Mary M, Tang, Jun, Lu, Yue, Rudnicki, Jean, Manninen, Aki, Matlin, Karl S
• Format: Article
• Language: English
• Subjects: Animals; Cell Adhesion; Cell Movement; Cell Polarity; Cells, Cultured; Dogs; Epithelial Cells - metabolism; Epithelial Cells - physiology; Gene Expression; Gene Knockdown Techniques; Integrin alpha3beta1 - metabolism; Integrin alpha6beta4 - metabolism; Kidney - cytology; Laminin - genetics; Laminin - metabolism; Microscopy, Video; Protein Binding; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Transport; RNA Interference; Time-Lapse Imaging
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E11-08-0718

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.