Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK

被引:173
作者
Bays, Jennifer L. [1 ]
Campbell, Hannah K. [1 ]
Heidema, Christy [2 ]
Sebbagh, Michael [3 ]
DeMali, Kris A. [1 ,2 ]
机构
[1] Univ Iowa, Dept Biochem, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
[2] Univ Iowa, Interdisciplinary Grad Program Mol & Cellular Bio, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
[3] Aix Marseille Univ UM105, Ctr Rech Cancerol Marseille, Inst Paoli Calmettes, UMR7258,CNRS,U1068,INSERM,Cell Signalling & Canc, F-13273 Marseille, France
基金
美国国家卫生研究院;
关键词
PROTEIN-KINASE; ACTIN POLYMERIZATION; ALPHA-CATENIN; RHO-KINASE; MECHANICAL TENSION; ADHERENS JUNCTIONS; TIGHT JUNCTIONS; SMOOTH-MUSCLE; SHEAR-STRESS; ADHESION;
D O I
10.1038/ncb3537
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The response of cells to mechanical force(1-3) is a major determinant of cell behaviour and is an energetically costly event(4,5). How cells derive energy to resist mechanical force is unknown. Here, we show that application of force to E-cadherin stimulates liver kinase B1 (LKB1) to activate AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. LKB1 recruits AMPK to the E-cadherin mechanotransduction complex, thereby stimulating actomyosin contractility, glucose uptake and ATP production. The increase in ATP provides energy to reinforce the adhesion complex and actin cytoskeleton so that the cell can resist physiological forces. Together, these findings reveal a paradigm for how mechanotransduction and metabolism are linked and provide a framework for understanding how diseases involving contractile and metabolic disturbances arise.
引用
收藏
页码:724 / +
页数:17
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