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AMPK: A Novel Link Between E‐cadherin Mechanotransduction And Cell Metabolism
Author(s) -
DeMali Kris,
Bays Jennifer,
Miller Hannah,
Heidema Christy
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.9.2
Subject(s) - ampk , mechanotransduction , microbiology and biotechnology , contractility , cadherin , energy homeostasis , regulator , protein kinase a , cell , cytoskeleton , amp activated protein kinase , cell metabolism , chemistry , kinase , biology , endocrinology , biochemistry , receptor , gene
The response of cells to mechanical force is a major determinant of cell behavior and is an energetically costly event. How the cell derives 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 increased ATP provides energy for reinforcing 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 with contractility and metabolic disturbances arise. Support or Funding Information Research reported in this publication was supported by The National Institutes of General Medicine (Award Number R01GM112805 to K.A.D) and the National Cancer Institute of the National Institutes of Health (Award Number P30CA086862). Predoctoral fellowships from the American Heart Association (Award Number AHA 16PRE26701111) and National Institutes of Health (Award T32 GM067795) support J.B. and C.H., respectively.