The cytoplasmic domain of neuropilin-1 regulates focal adhesion turnover

Though the vascular endothelial growth factor coreceptor neuropilin-1 (Nrp1) plays a critical role in vascular development, its precise function is not fully understood. We identified a group of novel binding partners of the cytoplasmic domain of Nrp1 that includes the focal adhesion regulator, Filamin A (FlnA). Endothelial cells (ECs) expressing a Nrp1 mutant devoid of the cytoplasmic domain (nrp1(cyto Delta)/Delta) migrated significantly slower in response to VEGF relative to the cells expressing wild-type Nrp1 (nrp1(+/+) cells). The rate of FA turnover in VEGF-treated nrp1(cyto Delta/Delta) ECs was an order of magnitude lower in comparison to nrp1(+/+) ECs, thus accounting for the slower migration rate of the nrp1(cyto Delta/Delta) ECs. summary of protein interactions: NRP1 physically interacts with alpha enolase, Myh10, Myh9, EEF1alpha1 and FlnA by anti bait coimmunoprecipitation (View interaction) FlnA and NRP1 colocalize by fluorescence microscopy (View interaction) NRP1 and rab11 colocalize by fluorescence microscopy (View interaction) NRP1 physically interacts with Myh10, Dync1h1, Myh9 and EEF1alpha1 by anti bait coimmunoprecipitation (View interaction) NRP1 and FlnA bind by isothermal titration calorimetry (View interaction) NRP1 physically interacts with p130Cas by anti bait coimmunoprecipitation (View interaction) NRP1 and p130Cas colocalize by fluorescence microscopy (View interaction) NRP1 binds to FlnA by surface plasmon resonance (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.