EVL is a novel focal adhesion protein involved in the regulation of cytoskeletal dynamics and vascular permeability

Joseph B. Mascarenhas, Amir A. Gaber, Tania M. Larrinaga, Rachel Mayfield, Stefanie Novak, Sara M. Camp, Carol Gregorio, Jeffrey R. Jacobson, Anne E. Cress, Steven M. Dudek, Joe GN Garcia

Research output: Contribution to journalArticlepeer-review

Abstract

Increases in lung vascular permeability is a cardinal feature of inflammatory disease and represents an imbalance in vascular contractile forces and barrier-restorative forces, with both forces highly dependent upon the actin cytoskeleton. The current study investigates the role of Ena-VASP-like (EVL), a member of the Ena-VASP family known to regulate the actin cytoskeleton, in regulating vascular permeability responses and lung endothelial cell barrier integrity. Utilizing changes in transendothelial electricial resistance (TEER) to measure endothelial cell barrier responses, we demonstrate that EVL expression regulates endothelial cell responses to both sphingosine-1-phospate (S1P), a vascular barrier-enhancing agonist, and to thrombin, a barrier-disrupting stimulus. Total internal reflection fluorescence demonstrates that EVL is present in endothelial cell focal adhesions and impacts focal adhesion size, distribution, and the number of focal adhesions generated in response to S1P and thrombin challenge, with the focal adhesion kinase (FAK) a key contributor in S1P-stimulated EVL-transduced endothelial cell but a limited role in thrombin-induced focal adhesion rearrangements. In summary, these data indicate that EVL is a focal adhesion protein intimately involved in regulation of cytoskeletal responses to endothelial cell barrier-altering stimuli. Keywords: cytoskeleton, vascular barrier, sphingosine-1-phosphate, thrombin, focal adhesion kinase (FAK), Ena-VASP like protein (EVL), cytoskeletal regulatory protein

Original languageEnglish (US)
JournalPulmonary Circulation
Volume11
Issue number4
DOIs
StatePublished - 2021

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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