Department of Molecular Cardiology, Lerner Research Institute, the Cleveland Clinic, Cleveland, OH 44195, United States.
FEBS Lett. 2013 Nov 1;587(21):3392-9. doi: 10.1016/j.febslet.2013.08.040. Epub 2013 Sep 8.
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.
虽然血管内皮生长因子核心受体神经纤毛蛋白-1(Nrp1)在血管发育中起着关键作用,但它的确切功能尚不完全清楚。我们鉴定了一组 Nrp1 胞质域的新结合伴侣,其中包括黏着斑调节因子细丝蛋白 A(FlnA)。与表达野生型 Nrp1(nrp1(+/+) 细胞)的细胞相比,表达无胞质域 Nrp1 突变体(nrp1(cyto)(Δ/Δ))的内皮细胞(EC)对 VEGF 的迁移速度明显较慢。与 nrp1(+/+) EC 相比,VEGF 处理的 nrp1(cyto)(Δ/Δ) EC 中的 FA 周转率低一个数量级,这解释了 nrp1(cyto)(Δ/Δ) EC 迁移速度较慢的原因。