Pellet-Many Caroline, Frankel Paul, Jia Haiyan, Zachary Ian
Centre for Cardiovascular Science and Medicine, Department of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK.
Biochem J. 2008 Apr 15;411(2):211-26. doi: 10.1042/BJ20071639.
NRPs (neuropilins) are co-receptors for class 3 semaphorins, polypeptides with key roles in axonal guidance, and for members of the VEGF (vascular endothelial growth factor) family of angiogenic cytokines. They lack a defined signalling role, but are thought to mediate functional responses as a result of complex formation with other receptors, such as plexins in the case of semaphorins and VEGF receptors (e.g. VEGFR2). Mutant mouse studies show that NRP1 is essential for neuronal and cardiovascular development, whereas NRP2 has a more restricted role in neuronal patterning and lymphangiogenesis, but recent findings indicate that NRPs may have additional biological roles in other physiological and disease-related settings. In particular, NRPs are highly expressed in diverse tumour cell lines and human neoplasms and have been implicated in tumour growth and vascularization in vivo. However, despite the wealth of information regarding the probable biological roles of these molecules, many aspects of the regulation of cellular function via NRPs remain uncertain, and little is known concerning the molecular mechanisms through which NRPs mediate the functions of their various ligands in different cell types.
神经纤毛蛋白（NRPs）是3类信号素的共受体，信号素是在轴突导向中起关键作用的多肽，同时也是血管生成细胞因子血管内皮生长因子（VEGF）家族成员的共受体。它们缺乏明确的信号传导作用，但被认为可通过与其他受体形成复合物来介导功能反应，例如在信号素的情况下与丛状蛋白以及VEGF受体（如VEGFR2）形成复合物。突变小鼠研究表明，NRP1对神经元和心血管发育至关重要，而NRP2在神经元模式形成和淋巴管生成中的作用更为局限，但最近的研究结果表明，NRPs可能在其他生理和疾病相关环境中具有额外的生物学作用。特别是，NRPs在多种肿瘤细胞系和人类肿瘤中高度表达，并与体内肿瘤生长和血管形成有关。然而，尽管有大量关于这些分子可能的生物学作用的信息，但通过NRPs调节细胞功能的许多方面仍不确定，关于NRPs在不同细胞类型中介导其各种配体功能的分子机制也知之甚少。
