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.
Journal Article
[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
Functional atlas of the integrin adhesome
TL;DR: Examination of the adhesome network motifs reveals a relatively small number of key motifs, dominated by three-component complexes in which a scaffolding molecule recruits both a signalling molecule and its downstream target.
Journal ArticleDOI
Integrins in angiogenesis and lymphangiogenesis
TL;DR: The evidence implicating integrins as a family of fundamental regulators of angiogenesis and lymphangiogenesis is reviewed, and several integrin-targeted therapeutic agents are currently in clinical trials for cancer therapy.
Journal ArticleDOI
Actin and alpha-actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor-independent manner.
Colin K. Choi,Miguel Vicente-Manzanares,Jessica Zareno,Leanna Whitmore,Alex Mogilner,Alan Rick Horwitz +5 more
TL;DR: A model for adhesion assembly is developed that clarifies the relative contributions of myosin II and actin polymerization and organization and produces a model that shows that nascent adhesions assemble and are stable within the lamellipodium.
Journal ArticleDOI
A practical guide to the MaxQuant computational platform for SILAC-based quantitative proteomics
Jürgen Cox,Ivan Matic,Maximiliane Hilger,Nagarjuna Nagaraj,Matthias Selbach,Jesper V. Olsen,Matthias Mann +6 more
TL;DR: This protocol explains step by step how to use MaxQuant on stable isotope labeling by amino acids in cell culture (SILAC) data obtained with double or triple labeling.
Journal Article
[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.