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Linking E-cadherin mechanotransduction to cell metabolism through force-mediated activation of AMPK
Journal article   Peer reviewed

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

Jennifer Bays, Hannah Campbell, Christy Heidema, Michael Sebbagh and Kris DeMali
Nature cell biology, Vol.19(6), pp.724-731
05/29/2017
DOI: 10.1038/ncb3537
PMCID: PMC5494977
PMID: 28553939
url
https://hal.science/hal-01785438View
Open Access

Abstract

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.
Life Sciences Molecular biology Biochemistry, Molecular Biology

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