β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments
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β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. / Schiller, Herbert B; Hermann, Michaela-Rosemarie; Polleux, Julien; Vignaud, Timothée; Zanivan, Sara; Friedel, Caroline C; Sun, Zhiqi; Raducanu, Aurelia; Gottschalk, Kay-E; Théry, Manuel; Mann, Matthias; Fässler, Reinhard.
In: Nature Cell Biology, Vol. 15, No. 6, 06.2013, p. 625-36.Research output: Contribution to journal › Journal article › Research
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TY - JOUR
T1 - β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments
AU - Schiller, Herbert B
AU - Hermann, Michaela-Rosemarie
AU - Polleux, Julien
AU - Vignaud, Timothée
AU - Zanivan, Sara
AU - Friedel, Caroline C
AU - Sun, Zhiqi
AU - Raducanu, Aurelia
AU - Gottschalk, Kay-E
AU - Théry, Manuel
AU - Mann, Matthias
AU - Fässler, Reinhard
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - Animals
KW - Antigens, CD29
KW - Carrier Proteins
KW - Cell Adhesion
KW - Cell Line
KW - Cell Movement
KW - Cellular Microenvironment
KW - Extracellular Matrix
KW - Extracellular Matrix Proteins
KW - Fibroblasts
KW - Fibronectins
KW - Focal Adhesions
KW - Guanine Nucleotide Exchange Factors
KW - Integrin alpha5beta1
KW - Integrin alphaV
KW - Male
KW - Mice
KW - Mice, Transgenic
KW - Myosin Type II
KW - Protein Binding
KW - Protein-Serine-Threonine Kinases
KW - Proto-Oncogene Proteins
KW - RNA Interference
KW - RNA, Small Interfering
KW - rho-Associated Kinases
KW - rhoA GTP-Binding Protein
U2 - 10.1038/ncb2747
DO - 10.1038/ncb2747
M3 - Journal article
C2 - 23708002
VL - 15
SP - 625
EP - 636
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 6
ER -
ID: 88583486