title: β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments.
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.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Schiller
authors.forename: Michaela-Rosemarie
authors.initials: MR
authors.lastname: Hermann
authors.forename: Julien
authors.initials: J
authors.lastname: Polleux
authors.forename: Timothée
authors.initials: T
authors.lastname: Vignaud
authors.forename: Sara
authors.initials: S
authors.lastname: Zanivan
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Friedel
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Sun
authors.forename: Aurelia
authors.initials: A
authors.lastname: Raducanu
authors.forename: Kay-E
authors.initials: KE
authors.lastname: Gottschalk
authors.forename: Manuel
authors.initials: M
authors.lastname: Théry
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D060833:Cellular Microenvironment; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D000080865:Formins; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039564:Integrin alphaV / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D024462:Myosin Type II / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D000080865:Formins; D020662:Guanine Nucleotide Exchange Factors; D039081:Integrin alpha5beta1; D039564:Integrin alphaV; D019012:Integrin beta1; D024462:Myosin Type II; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D064067:Rho Guanine Nucleotide Exchange Factors; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000099200:Scaffold Protein ILK; C577402:Arhgef2 protein, mouse; C491464:Diap1 protein, mouse