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Mechanisms Linking Mechanotransduction and Cell Metabolism
Author(s) -
DeMali Kris,
Salvi Alicia,
Bays Jennifer
Publication year - 2020
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.2020.34.s1.00150
Subject(s) - cytoskeleton , microbiology and biotechnology , ampk , glucose transporter , glut1 , actin cytoskeleton , actin , actin remodeling , chemistry , spectrin , adherens junction , cadherin , cell , biology , biochemistry , protein kinase a , kinase , endocrinology , insulin
External forces are sensed by cell surface adhesion receptors, such as E‐cadherin, and trigger robust actin cytoskeletal rearrangements that allow the cell to withstand the force. These actin rearrangements are energetically costly and require approximately half of the ATP in a cell. Previous work in our laboratory demonstrated that in response to force, E‐cadherin signals for enhanced energy production by stimulating AMP‐activated protein kinase (AMPK). AMPK triggers glucose uptake and its oxidation to ATP thereby providing the energy necessary for actin cytoskeletal remodeling. How mechanical force stimulates glucose uptake remains completely unexplored. In this study, we identify glucose transporter‐1 (GLUT1) as a force‐sensitive protein that is highly enriched in the plasma membrane in cells under tension. GLUT1 is necessary for the uptake of glucose and the reinforcement of the actin cytoskeleton that occurs when E‐cadherin experiences force. Intriguingly, GLUT1 is recruited to the cell‐cell junctions and forms a complex with E‐cadherin via a novel linkage mediated by the spectrin adaptor protein, Ankyrin G. Loss of Ankyrin G binding to E‐cadherin inhibits GLUT1 retention to the membrane, glucose uptake, and reinforcement of the actin cytoskeleton in response to force. This study provides the first mechanism for how cell mechanics stimulates the uptake of glucose. Support or Funding Information This work is supported by NIH Grant #GM112805.