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2017 ; 19
(6
): 724-731
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Linking E-cadherin mechanotransduction to cell metabolism through force-mediated
activation of AMPK
#MMPMID28553939
Bays JL
; Campbell HK
; Heidema C
; Sebbagh M
; DeMali KA
Nat Cell Biol
2017[Jun]; 19
(6
): 724-731
PMID28553939
show ga
The response of cells to mechanical force is a major determinant of cell
behaviour and is an energetically costly event. 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.
|*Energy Metabolism
[MESH]
|*Mechanotransduction, Cellular
[MESH]
|AMP-Activated Protein Kinase Kinases
[MESH]
|AMP-Activated Protein Kinases/genetics/*metabolism
[MESH]