The integrin-ligand interaction regulates adhesion and migration through a molecular clutch
Entity
UAM. Departamento de MedicinaPublisher
Public Library of ScienceDate
2012-07-06Citation
10.1371/journal.pone.0040202
Plos One 7.7 (2012): e40202
ISSN
1932-6203 (online)DOI
10.1371/journal.pone.0040202Funded by
ARH was supported by National Institutes of Health grants GM23244 and the Cell Migration Consortium (U54 GM064346). MVM is supported by the Ramon y Cajal program (RYC-2010-06094) from the Spanish Ministerio de Economía y Competividad (MINECO). PWW acknowledges funding support from the Natural Sciences and Engineering Council of Canada (NSERC) and the Canadian Institutes of Health Research. LPT acknowledges fellowship support from Fonds québécois de la recherche sur la nature et les technologies (FQRNT) and NSERCSubjects
Cell Movement; Gene Expression; Leukocytes; Protein Transport; Integrins; MedicinaRights
© 2012 Chen et al.Abstract
Adhesive and migratory behavior can be cell type, integrin, and substrate dependent. We have compared integrin and substrate differences using three integrin receptors: α5β1, α6β1, and αLβ2 expressed in a common cell type, CHO.B2 cells, which lack integrin α subunits, as well as in different cell types that express one or more of these integrins. We find that CHO.B2 cells expressing either α6β1 or αLβ2 integrins migrate and protrude faster and are more directionally persistent on laminin or ICAM-1, respectively, than CHO.B2 cells expressing α5β1 on fibronectin. Despite rapid adhesion maturation and the presence of large adhesions in both the α6β1- and αLβ2-expressing cells, they display robust tyrosine phosphorylation. In addition, whereas myosin II regulates adhesion maturation and turnover, protrusion rates, and polarity in cells migrating on fibronectin, surprisingly, it does not have comparable effects in cells expressing α6β1 or αLβ2. This apparent difference in the integration of myosin II activity, adhesion, and migration arises from alterations in the ligand-integrin-actin linkage (molecular clutch). The elongated adhesions in the protrusions of the α6β1-expressing cells on laminin or the αLβ2-expressing cells on ICAM-1 display a novel, rapid retrograde flux of integrin; this was largely absent in the large adhesions in protrusions of α5β1-expressing cells on fibronectin. Furthermore, the force these adhesions exert on the substrate in protrusive regions is reduced compared to similar regions in α5-expressing cells, and the adhesion strength is reduced. This suggests that intracellular forces are not efficiently transferred from actomyosin to the substratum due to altered adhesion strength, that is, avidity, affinity, or the ligand-integrin-actin interaction. Finally, we show that the migration of fast migrating leukocytes on fibronectin or ICAM-1 is also largely independent of myosin II; however, their adhesions are small and do not show retrograde fluxing suggesting other intrinsic factors determine their migration differences
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Google Scholar:Chen, Lingfeng
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Vicente-Manzanares, Miguel
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Potvin-Trottier, Laurent
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Wiseman, Paul W.
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Horwitz, Alan Rick
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