Journal ArticleDOI
β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments.
Herbert B. Schiller,Michaela-Rosemarie Hermann,Julien Polleux,Timothée Vignaud,Sara Zanivan,Caroline C. Friedel,Zhiqi Sun,Aurelia Raducanu,Kay-E. Gottschalk,Manuel Théry,Matthias Mann,Reinhard Fässler +11 more
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TLDR
This 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.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.read more
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Mechanotransduction and extracellular matrix homeostasis
TL;DR: Progress towards understanding the molecular, cellular and tissue-level effects that promote mechanical homeostasis has helped to identify key questions for future research.
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[Expression of fusion proteins in beta(2)GP I gene-transfected HEp-2 cells and its clinical application].
Liangjing Lu,Shunle Chen,Yue-ying Gu,Nan Shen,Chunde Bao,Yuan Wang,Chengde Yang,Ping Ye,Chong-zhao Yu +8 more
TL;DR: As a new kind of substrate of IIF, beta( 2)GP I transfectant can be used to detect anti-beta(2)GP-I antibodies and keep the immunofluorescent property of HEp-2 cells in IFANA test and can be use as substrate for routine IFANA detection.
Journal ArticleDOI
Integrin-mediated mechanotransduction.
TL;DR: Sun, Guo, and Fässler review the function and regulation of integrin-mediated mechanotransduction and discuss how its dysregulation impacts cancer progession.
Journal ArticleDOI
Integrins as biomechanical sensors of the microenvironment.
TL;DR: An overview of how integrin function is regulated from both a biochemical and a mechanical perspective, affecting integrin cell-surface availability, binding properties, activation or clustering is provided, and how this biomechanical regulation allows integrins to respond to different ECM physicochemical properties and signals.
Journal ArticleDOI
Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity
Alberto Elosegui-Artola,Roger Oria,Yunfeng Chen,Yunfeng Chen,Anita Joanna Kosmalska,Carlos Pérez-González,Natalia Castro,Cheng Zhu,Cheng Zhu,Xavier Trepat,Pere Roca-Cusachs +10 more
TL;DR: It is shown that in response to matrix rigidity and density, force transmission and transduction are explained by the mechanical properties of the actin–talin–integrin–fibronectin clutch.
References
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Journal ArticleDOI
The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins
Christophe Guilluy,Vinay Swaminathan,Rafael Garcia-Mata,E. Timothy O'Brien,Richard Superfine,Keith Burridge +5 more
TL;DR: Two guanine nucleotide exchange factors, LARG and GEF-H1, are identified as key molecules that regulate the cellular adaptation to force and stimulation of integrins with tensional force triggers activation of these two GEFs and their recruitment to adhesion complexes.
Journal ArticleDOI
Integrins β1 and β3 exhibit distinct dynamic nanoscale organizations inside focal adhesions.
Olivier Rossier,Vivien Octeau,Vivien Octeau,Jean-Baptiste Sibarita,Jean-Baptiste Sibarita,Cécile Leduc,Cécile Leduc,Béatrice Tessier,Béatrice Tessier,Deepak T. Nair,Deepak T. Nair,Volker Gatterdam,Olivier Destaing,Corinne Albiges-Rizo,Robert Tampé,Laurent Cognet,Laurent Cognet,Daniel Choquet,Daniel Choquet,Brahim Lounis,Brahim Lounis,Grégory Giannone,Grégory Giannone +22 more
TL;DR: Using single-protein tracking and super-resolution imaging, dynamic nano-organizations of integrins and talin inside FAs are revealed and differential transmission of actin motion to fibronectin occurs through specificIntegrins within FAs.
Journal ArticleDOI
Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src.
TL;DR: It is found that active ERK is targeted to newly forming focal adhesions after integrin engagement or activation of v‐Src, and this support a role for ERK in the regulation of the adhesion/cytoskeletal network and provide an explanation for the role of ERk in cell motility.
Journal ArticleDOI
Tension is required but not sufficient for focal adhesion maturation without a stress fiber template
TL;DR: Lamellar actin architecture at adhesion sites may serve as a structural template that facilitates focal adhesion maturation over a wide range of tension.
Journal ArticleDOI
The fibronectin-binding integrins α5β1 and αvβ3 differentially modulate RhoA–GTP loading, organization of cell matrix adhesions, and fibronectin fibrillogenesis
TL;DR: It is demonstrated that the pattern of fibronectin receptors expressed on a cell dictates the ability of fibronsectin to stimulate RhoA-mediated organization of cell matrix adhesions and that β1-mediated control of the levels of β3 is important for the distribution of focal contacts.