An Abl-FBP17 mechanosensing system couples local plasma membrane curvature and stress fiber remodeling during mechanoadaptation

Asier Echarri (), Dácil M. Pavón, Sara Sánchez, María García-García, Enrique Calvo, Carla Huerta-López, Diana Velázquez-Carreras, Christine Viaris de Lesegno, Nicholas Ariotti, Ana Lázaro-Carrillo, Raffaele Strippoli, David De Sancho, Jorge Alegre-Cebollada, Christophe Lamaze, Robert G. Parton and Miguel A. Del Pozo ()
Additional contact information
Asier Echarri: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Dácil M. Pavón: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Sara Sánchez: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
María García-García: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Enrique Calvo: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Carla Huerta-López: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Diana Velázquez-Carreras: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Christine Viaris de Lesegno: Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143
Nicholas Ariotti: The Institute for Molecular Bioscience, The University of Queensland
Ana Lázaro-Carrillo: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Raffaele Strippoli: Sapienza University
David De Sancho: Euskal Herriko Unibertsitatea
Jorge Alegre-Cebollada: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Christophe Lamaze: Institut Curie – Centre de Recherche, PSL Research University, CNRS UMR3666, INSERM U1143
Robert G. Parton: The Institute for Molecular Bioscience, The University of Queensland
Miguel A. Del Pozo: Centro Nacional de Investigaciones Cardiovasculares (CNIC)

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13782-2

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