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


ABSTRACT: 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 ?v?5 integrin, and is a consequence of frustrated endocytosis whereby ?v?5 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.

SUBMITTER: Baschieri F 

PROVIDER: S-EPMC6148028 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Baschieri Francesco F   Dayot Stéphane S   Elkhatib Nadia N   Ly Nathalie N   Capmany Anahi A   Schauer Kristine K   Betz Timo T   Vignjevic Danijela Matic DM   Poincloux Renaud R   Montagnac Guillaume G  

Nature communications 20180920 1


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 ass  ...[more]

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