ß1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments.
Nat Cell Biol
; 15(6): 625-36, 2013 Jun.
Article
en En
| MEDLINE
| ID: mdl-23708002
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 ß1- and αv-class integrins expressed in pan-integrin-null fibroblasts seeded on fibronectin. Reconstitution with ß1-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 α5ß1 integrins to a RhoA-Rock-myosin II pathway. Our study assigns specific functions to distinct fibronectin-binding integrins, demonstrating that α5ß1integrins 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibronectinas
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Integrina beta1
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Miosina Tipo II
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Integrina alfaV
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Microambiente Celular
Límite:
Animals
Idioma:
En
Revista:
Nat Cell Biol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Alemania