Affordable Access

deepdyve-link
Publisher Website

Drebrin preserves endothelial integrity by stabilizing nectin at adherens junctions.

Authors
  • Rehm, Kerstin
  • Panzer, Linda
  • van Vliet, Vanessa
  • Genot, Elisabeth
  • Linder, Stefan
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Aug 15, 2013
Volume
126
Issue
Pt 16
Pages
3756–3769
Identifiers
DOI: 10.1242/jcs.129437
PMID: 23750010
Source
Medline
Keywords
License
Unknown

Abstract

Regulation of cell-cell contacts is essential for integrity of the vascular endothelium. Here, a critical role of the F-actin-binding protein drebrin in maintaining endothelial integrity is revealed under conditions mimicking vascular flow. Drebrin knockdown leads to weakening of cell-cell contacts, characterized by loss of nectin from adherens junctions and its subsequent lysosomal degradation. Immunoprecipitation, FRAP and mitochondrial re-targeting experiments show that nectin stabilization occurs through a chain of interactions: drebrin binding to F-actin, interaction of drebrin and afadin through their polyproline and PR1-2 regions, and recruitment of nectin through the PDZ region of afadin. Key elements are modules in drebrin that confer binding to afadin and F-actin. Evidence for this was obtained using constructs containing the PDZ region of afadin coupled to the F-actin-binding region of drebrin or to lifeact, which restore junctional nectin under knockdown of drebrin or of both drebrin and afadin. Drebrin, containing binding sites for both afadin and F-actin, is thus uniquely equipped to stabilize nectin at endothelial junctions and to preserve endothelial integrity under vascular flow.

Report this publication

Statistics

Seen <100 times