Journal Article

Frustrated endocytosis controls contractility-independent mechanotransduction at clathrin-coated structures

Dayot, Stéphane, Schauer, Kristine, Baschieri, Francesco, Vignjevic, Danijela Matic, Montagnac, Guillaume, Elkhatib, Nadia, Capmany, Anahi, Poincloux, Renaud, Ly, Nathalie, Betz, Timo

2018

Overview

It is generally assumed that cells interrogate the mechanical properties of their environment by pushing and pulling on the extracellular matrix (ECM). For instance, acto-myosin-dependent contraction forces exerted at focal adhesions (FAs) allow the cell to actively probe substrate elasticity. Here, we report that a subset of long-lived and flat clathrin-coated structures (CCSs), also termed plaques, are contractility-independent mechanosensitive signaling platforms. We observed that plaques assemble in response to increasing substrate rigidity and that this is independent of FAs, actin and myosin-II activity. We show that plaque assembly depends on αvβ5 integrin, and is a consequence of frustrated endocytosis whereby αvβ5 tightly engaged with the stiff substrate locally stalls CCS dynamics. We also report that plaques serve as platforms for receptor-dependent signaling and are required for increased Erk activation and cell proliferation on stiff environments. We conclude that CCSs are mechanotransduction structures that sense substrate rigidity independently of cell contractility. Cells sense mechanical properties of their environment using various cellular structures including focal adhesions. Here, the authors identify flat clathrin-coated structures (CCSs) as mechanosensitive signaling platforms that form independently of contractility and in response to substrate rigidity.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14 / 14/19 / 631/80 / 631/80/79 / Actin / Cell activation / Cell growth / Cell Line / Cell Proliferation / Clathrin / Clathrin-Coated Vesicles - metabolism / Clathrin-Coated Vesicles - ultrastructure / Contractility / Contraction / Elasticity / Endocytosis / Extracellular matrix / Humanities and Social Sciences / Humans / Life Sciences / MAP Kinase Signaling System / Mechanical properties / Mechanotransduction / Mechanotransduction, Cellular / multidisciplinary / Myosin / Plaques / Platforms / Receptors, Vitronectin - metabolism / Rigidity / Scanning electron microscopy / Science / Science (multidisciplinary) / Signaling / Substrates