| First Author | Schiller HB | Year | 2013 |
| Journal | Nat Cell Biol | Volume | 15 |
| Issue | 6 | Pages | 625-36 |
| PubMed ID | 23708002 | Mgi Jnum | J:198991 |
| Mgi Id | MGI:5500089 | Doi | 10.1038/ncb2747 |
| Citation | Schiller HB, et al. (2013) beta1- and alphav-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. Nat Cell Biol 15(6):625-36 |
| abstractText | How different integrins that bind to the same type of extracellular matrix protein mediate specific functions is unclear. We report the functional analysis of beta1- and alphav-class integrins expressed in pan-integrin-null fibroblasts seeded on fibronectin. Reconstitution with beta1-class integrins promotes myosin-II-independent formation of small peripheral adhesions and cell protrusions, whereas expression of alphav-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 alphav-class integrins accumulating in adhesion areas exposed to high traction forces. Quantitative proteomics linked alphav-class integrins to a GEF-H1-RhoA pathway coupled to the formin mDia1 but not myosin II, and alpha5beta1 integrins to a RhoA-Rock-myosin II pathway. Our study assigns specific functions to distinct fibronectin-binding integrins, demonstrating that alpha5beta1integrins accomplish force generation, whereas alphav-class integrins mediate the structural adaptations to forces, which cooperatively enable cells to sense the rigidity of fibronectin-based microenvironments. |
