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)(Δ/Δ)) 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)(Δ/Δ) ECs was an order of magnitude lower in comparison to nrp1(+/+) ECs, thus accounting for the slower migration rate of the nrp1(cyto)(Δ/Δ) ECs.
Keywords: Cytoplasmic domain; Filamin A; Focal adhesion; Neuropilin-1.
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