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

被引:75
作者
Baschieri, Francesco [1 ]
Dayot, Stephane [1 ,5 ]
Elkhatib, Nadia [1 ]
Ly, Nathalie [1 ]
Capmany, Anahi [2 ]
Schauer, Kristine [2 ]
Betz, Timo [3 ]
Vignjevic, Danijela Matic [2 ]
Poincloux, Renaud [4 ]
Montagnac, Guillaume [1 ]
机构
[1] Univ Paris Saclay, INSERM, U1170, Gustave Roussy Inst, Villejuif, France
[2] PSL Res Univ, CNRS, Ctr Univ, Inst Curie,UMR144, Paris, France
[3] Univ Munster, Cells Mot Cluster Excellence, Ctr Mol Biol Inflammat, Inst Cell Biol, Munster, Germany
[4] Univ Toulouse, CNRS, Inst Pharmacol & Biol Struct, IPBS,UPS, Toulouse, France
[5] PSL Res Univ, INSERM, Ctr Univ, Inst Curie,U830, Paris, France
来源
NATURE COMMUNICATIONS | 2018年 / 9卷
关键词
CYTOPLASMIC DOMAIN; VITRONECTIN; RECEPTOR; INTEGRINS; GROWTH; SOFT; ALPHA-V-BETA-3; FORCE;
D O I
10.1038/s41467-018-06367-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 av beta 5 integrin, and is a consequence of frustrated endocytosis whereby av beta 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.
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页数:13
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