학술논문

An Abl-FBP17 mechanosensing system couples local plasma membrane curvature and stress fiber remodeling during mechanoadaptation.
Document Type
Academic Journal
Author
Echarri A; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain. aecharri@cnic.es.; Pavón DM; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain.; Sánchez S; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain.; García-García M; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain.; Calvo E; Proteomics Unit, Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain.; Huerta-López C; Molecular Mechanics of the Cardiovascular System Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain.; Velázquez-Carreras D; Molecular Mechanics of the Cardiovascular System Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain.; Viaris de Lesegno C; Membrane Mechanics and Dynamics of Intracellular Signaling Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, 75248, Paris, France.; Ariotti N; The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.; Lázaro-Carrillo A; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain.; Departamento de Biología, Universidad Autónoma de Madrid, Cantoblanco, 28049, Madrid, Spain.; Strippoli R; Department of Molecular Medicine, Sapienza University, Rome, Italy.; De Sancho D; Departamento de Ciencia y Tecnología de Polímeros, Euskal Herriko Unibertsitatea, 20018, Donostia-San Sebastián, Spain.; Donostia International Physics Center, Manuel Lardizabal Ibilbidea, 4, 20018, Donostia-San Sebastián, Spain.; Alegre-Cebollada J; Molecular Mechanics of the Cardiovascular System Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain.; Lamaze C; Membrane Mechanics and Dynamics of Intracellular Signaling Laboratory, Institut Curie - Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143, 75248, Paris, France.; Parton RG; The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.; The Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane, QLD, 4072, Australia.; Del Pozo MA; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029, Madrid, Spain. madelpozo@cnic.es.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
Abstract
Cells remodel their structure in response to mechanical strain. However, how mechanical forces are translated into biochemical signals that coordinate the structural changes observed at the plasma membrane (PM) and the underlying cytoskeleton during mechanoadaptation is unclear. Here, we show that PM mechanoadaptation is controlled by a tension-sensing pathway composed of c-Abl tyrosine kinase and membrane curvature regulator FBP17. FBP17 is recruited to caveolae to induce the formation of caveolar rosettes. FBP17 deficient cells have reduced rosette density, lack PM tension buffering capacity under osmotic shock, and cannot adapt to mechanical strain. Mechanistically, tension is transduced to the FBP17 F-BAR domain by direct phosphorylation mediated by c-Abl, a mechanosensitive molecule. This modification inhibits FBP17 membrane bending activity and releases FBP17-controlled inhibition of mDia1-dependent stress fibers, favoring membrane adaptation to increased tension. This mechanoprotective mechanism adapts the cell to changes in mechanical tension by coupling PM and actin cytoskeleton remodeling.