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Mechanical activation of VE-cadherin stimulates AMPK to increase endothelial cell metabolism and vasodilation
Preprint   Open access

Mechanical activation of VE-cadherin stimulates AMPK to increase endothelial cell metabolism and vasodilation

Nicholas M Cronin, Logan W Dawson and Kris A DeMali
bioRxiv : the preprint server for biology
Cold Spring Harbor Laboratory
05/13/2024
DOI: 10.1101/2024.05.09.593171
PMCID: PMC11118335
PMID: 38798670
url
https://doi.org/10.1101/2024.05.09.593171View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Endothelia cells respond to mechanical force by stimulating cellular signaling, but how these pathways are linked to elevations in cell metabolism and whether metabolism supports the mechanical response remains poorly understood. Here, we show that application of force to VE-cadherin stimulates liver kinase B1 (LKB1) to activate AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. VE-cadherin stimulated AMPK increases eNOS activity and localization to the plasma membrane as well as reinforcement of the actin cytoskeleton and cadherin adhesion complex, and glucose uptake. We present evidence for the increase in metabolism being necessary to fortify the adhesion complex, actin cytoskeleton, and cellular alignment. Together these data extend the paradigm for how mechanotransduction and metabolism are linked to include a connection to vasodilation, thereby providing new insight into how diseases involving contractile, metabolic, and vasodilatory disturbances arise.

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