The ability to form a variety of cell-matrix connections is crucial for angiogenesis to take place. Without stable anchorage to the extracellular matrix (ECM), endothelial cells (ECs) are unable to sense, integrate and disseminate growth factor stimulated responses that drive growth of a vascular bed. Neuropilin-2 (NRP2) is a widely expressed membrane-bound multifunctional non-tyrosine kinase receptor, that has previously been implicated in influencing cell adhesion and migration by interacting with α5-integrin and regulating adhesion turnover. α5-integrin, and its ECM ligand fibronectin (FN) are both known to be upregulated during the formation of neo-vasculature. Despite being descriptively annotated as a candidate biomarker for aggressive cancer phenotypes, the EC-specific roles for NRP2 during developmental and pathological angiogenesis remain unexplored. The data reported here support a model whereby NRP2 actively promotes EC adhesion and migration by regulating dynamic cytoskeletal remodelling and by stimulating Rab11-dependent recycling of α5-integrin-p-FAK complexes to newly assembling adhesion sites. Furthermore, temporal depletion of EC-NRP2 in vivo impairs primary tumour growth by disrupting vessel formation. We also demonstrate that EC-NRP2 is required for normal postnatal retinal vascular development, specifically by regulating cell-matrix adhesion. Upon loss of endothelial NRP2, vascular outgrowth from the optic nerve during superficial plexus formation is disrupted, likely due to reduced FAK phosphorylation within sprouting tip cells.

中文翻译：

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内皮NRP2通过调节肌动蛋白模式发展和α5-整合素-p-FAK复合物募集以组装黏附位点来影响血管生成。

形成多种细胞-基质连接的能力对于发生血管生成至关重要。没有稳定的锚定到细胞外基质（ECM），内皮细胞（EC）无法感知，整合和传播驱动血管床生长的生长因子刺激的反应。Neuropilin-2（NRP2）是一种广泛表达的膜结合多功能非酪氨酸激酶受体，以前与α5-integrin相互作用并调节粘附转换影响了细胞粘附和迁移。众所周知，α5-整联蛋白及其ECM配体纤连蛋白（FN）在新脉管系统形成过程中均被上调。尽管被描述性地标记为侵略性癌症表型的候选生物标志物，在发育和病理性血管生成过程中，NRP2的EC特异性作用尚待探索。此处报道的数据支持了一种模型，其中NRP2通过调节动态细胞骨架重塑以及刺激Rab11依赖的α5-整合素-p-FAK复合物向新组装的粘附位点的循环而积极促进EC粘附和迁移。此外，体内EC-NRP2的暂时耗竭会通过破坏血管形成而损害原发性肿瘤的生长。我们还证明，正常的产后视网膜血管发育需要EC-NRP2，特别是通过调节细胞-基质粘附。内皮NRP2丢失后，浅神经丛形成过程中视神经的血管生长受到破坏，这可能是由于发芽尖端细胞内FAK磷酸化的降低所致。此处报道的数据支持了一种模型，其中NRP2通过调节动态细胞骨架重塑以及刺激Rab11依赖的α5-整合素-p-FAK复合物向新组装的粘附位点的循环而积极促进EC粘附和迁移。此外，体内EC-NRP2的暂时耗竭会通过破坏血管形成而损害原发性肿瘤的生长。我们还证明，正常的产后视网膜血管发育需要EC-NRP2，特别是通过调节细胞-基质粘附。内皮NRP2丢失后，浅神经丛形成过程中视神经的血管生长受到破坏，这可能是由于发芽尖端细胞内FAK磷酸化的降低所致。此处报道的数据支持了一种模型，其中NRP2通过调节动态细胞骨架重塑以及刺激Rab11依赖的α5-整合素-p-FAK复合物向新组装的粘附位点的循环而积极促进EC粘附和迁移。此外，体内EC-NRP2的暂时耗竭会通过破坏血管形成而损害原发性肿瘤的生长。我们还证明，正常的产后视网膜血管发育需要EC-NRP2，特别是通过调节细胞-基质粘附。内皮NRP2丢失后，浅神经丛形成过程中视神经的血管生长受到破坏，这可能是由于发芽尖端细胞内FAK磷酸化的降低所致。