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

BASCHIERI, FRANCESCO; DAYOT, STÉPHANE; ELKHATIB, NADIA; LY, NATHALIE; CAPMANY, ANAHI; SCHAUER, KRISTINE; BETZ, TIMO; VIGNJEVIC, DANIJELA MATIC; POINCLOUX, RENAUD; MONTAGNAC, GUILLAUME

NATURE COMMUNICATIONS

Nature Publishing Group

Lugar: London; Año: 2018 vol. 9

2041-1723

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.