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

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  • D. Stephen Serafin

    (University of North Carolina at Chapel Hill)

  • Natalie R. Harris

    (University of North Carolina at Chapel Hill)

  • László Bálint

    (University of North Carolina at Chapel Hill)

  • Elizabeth S. Douglas

    (University of North Carolina at Chapel Hill)

  • Kathleen M. Caron

    (University of North Carolina at Chapel Hill)

Abstract

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.

Suggested Citation

  • D. Stephen Serafin & Natalie R. Harris & László Bálint & Elizabeth S. Douglas & Kathleen M. Caron, 2024. "Proximity interactome of lymphatic VE-cadherin reveals mechanisms of junctional remodeling and reelin secretion," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51918-1
    DOI: 10.1038/s41467-024-51918-1
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    1. Xiaolei Liu & Ester Cruz & Xiaowu Gu & Laszlo Balint & Michael Oxendine-Burns & Tamara Terrones & Wanshu Ma & Hui-Hsuan Kuo & Connor Lantz & Trisha Bansal & Edward Thorp & Paul Burridge & Zoltán Jakus, 2020. "Lymphoangiocrine signals promote cardiac growth and repair," Nature, Nature, vol. 588(7839), pages 705-711, December.
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