Laminin 511 partners with laminin 332 to mediate directional migration of Madin-Darby canine kidney epithelial cells.
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.
Department of Surgery and Committee on Molecular Medicine, University of Chicago, Chicago, IL 60637, USA. pgonzale1@surgery.bsd.uchicago.edu
Patricia G
PG
Greciano
Jose V
JV
Moyano
Mary M
MM
Buschmann
Jun
J
Tang
Yue
Y
Lu
Jean
J
Rudnicki
Aki
A
Manninen
Karl S
KS
Matlin
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D039201:Integrin alpha3beta1 / Q000378:metabolism; D039161:Integrin alpha6beta4 / Q000378:metabolism; D007668:Kidney / Q000166:cytology*; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D018715:Microscopy, Video; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D059008:Time-Lapse Imaging
D039201:Integrin alpha3beta1; D039161:Integrin alpha6beta4; D007797:Laminin; D020033:Protein Isoforms; C097043:laminin alpha5; C095567:laminin alpha 3