Migration of epithelial cells on laminins: RhoA antagonizes directionally persistent migration.
Spatial and temporal expression of laminin isoforms is assumed to provide specific local information to neighboring cells. Here, we report the remarkably selective presence of LM-111 at the very tip of hair follicles where LM-332 is absent, suggesting that epithelial cells lining the dermal-epidermal junction at this location may receive different signals from the two laminins. This hypothesis was tested in vitro by characterizing with functional and molecular assays the comportment of keratinocytes exposed to LM-111 and LM-332. The two laminins induced morphologically distinct focal adhesions, and LM-332, but not LM-111, elicited persistent migration of keratinocytes. The different impact on cellular behavior was associated with distinct activation patterns of Rho GTPases and other signaling intermediates. In particular, while LM-111 triggered a robust activation of Cdc42, LM-332 provoked a strong and sustained activation of FAK. Interestingly, activation of Rac1 was necessary but not sufficient to promote migration because there was no directed migration on LM-111 despite Rac1 activation. In contrast, RhoA antagonized directional migration, since silencing of RhoA by RNA interference boosted unidirectional migration on LM-332. Molecular analysis of the role of RhoA strongly suggested that the mechanisms involve disassembly of cell-cell contacts, loss of the cortical actin network, mobilization of α6β4 integrin out of stable adhesions, and displacement of the integrin from its association with the insoluble pool of intermediate filaments.
Zhang
Zhigang
Z
Center for Biochemistry, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Cologne, Germany.
Chometon
Gretel
G
Wen
Tingting
T
Qu
Haiyan
H
Mauch
Cornelia
C
Krieg
Thomas
T
Aumailley
Monique
M
D002460:Cell Line; D002465:Cell Movement; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015870:Gene Expression; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D016023:Integrins / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology*; D007797:Laminin / Q000235:genetics / Q000502:physiology*; D008853:Microscopy; D034622:RNA Interference; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D016023:Integrins; D007797:Laminin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein