β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments

Schiller, H.B. et al. (2013) β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. Nature Cell Biology, 15(6), pp. 625-636. (doi:10.1038/ncb2747)

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Abstract

How different integrins that bind to the same type of extracellular matrix protein mediate specific functions is unclear. We report the functional analysis of β1- and αv-class integrins expressed in pan-integrin-null fibroblasts seeded on fibronectin. Reconstitution with β1-class integrins promotes myosin-II-independent formation of small peripheral adhesions and cell protrusions, whereas expression of αv-class integrins induces the formation of large focal adhesions. Co-expression of both integrin classes leads to full myosin activation and traction-force development on stiff fibronectin-coated substrates, with αv-class integrins accumulating in adhesion areas exposed to high traction forces. Quantitative proteomics linked αv-class integrins to a GEF-H1–RhoA pathway coupled to the formin mDia1 but not myosin II, and α5β1 integrins to a RhoA–Rock–myosin II pathway. Our study assigns specific functions to distinct fibronectin-binding integrins, demonstrating that α5β1integrins accomplish force generation, whereas αv-class integrins mediate the structural adaptations to forces, which cooperatively enable cells to sense the rigidity of fibronectin-based microenvironments.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Zanivan, Dr Sara Rossana
Authors: Schiller, H.B., Hermann, M., Polleux, J., Vignaud, T., Zanivan, S., Friedel, C.C., Sun, Z., Raducanu, A., Gottschalk, K.-E., Théry, M., Mann, M., and Fässler, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Cell Biology
ISSN:1465-7392
ISSN (Online):1476-4679

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