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 & Miguel A. Del Pozo

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.

Referencia: Echarri, A., Pavón, D.M., Sánchez, S. et al. An Abl-FBP17 mechanosensing system couples local plasma membrane curvature and stress fiber remodeling during mechanoadaptation. Nat Commun 10, 5828 (2019) doi:10.1038/s41467-019-13782-2

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