Proximity interactome of lymphatic VE-cadherin reveals mechanisms of junctional remodeling and reelin secretion.

Autor: Serafin DS; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, 27599, NC, USA., Harris NR; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, 27599, NC, USA., Bálint L; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, 27599, NC, USA., Douglas ES; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, 27599, NC, USA., Caron KM; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, 27599, NC, USA. kathleen_caron@med.unc.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 04; Vol. 15 (1), pp. 7734. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1038/s41467-024-51918-1
Abstrakt: The adhesion receptor vascular endothelial (VE)-cadherin transduces an array of signals that modulate crucial lymphatic cell behaviors including permeability and cytoskeletal remodeling. Consequently, VE-cadherin must interact with a multitude of intracellular proteins to exert these functions. Yet, the full protein interactome of VE-cadherin in endothelial cells remains a mystery. Here, we use proximity proteomics to illuminate how the VE-cadherin interactome changes during junctional reorganization from dis-continuous to continuous junctions, triggered by the lymphangiogenic factor adrenomedullin. These analyses identified interactors that reveal roles for ADP ribosylation factor 6 (ARF6) and the exocyst complex in VE-cadherin trafficking and recycling. We also identify a requisite role for VE-cadherin in the in vitro and in vivo control of secretion of reelin-a lymphangiocrine glycoprotein with recently appreciated roles in governing heart development and injury repair. This VE-cadherin protein interactome shines light on mechanisms that control adherens junction remodeling and secretion from lymphatic endothelial cells.
(© 2024. The Author(s).)
Databáze: MEDLINE
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