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J Cell Sci. 2013 Aug 15;126(Pt 16):3756-69. doi: 10.1242/jcs.129437. Epub 2013 Jun 7.

Drebrin preserves endothelial integrity by stabilizing nectin at adherens junctions.

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Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.


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.


Actin cytoskeleton; Afadin; Cell–cell junctions; Drebrin; Endothelial cells; Nectin

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