Tao Qi, Spring Simone C, Terman Bruce I
Cardiology Division, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Angiogenesis. 2003;6(1):39-45. doi: 10.1023/a:1025884628155.
Neuropilin-1 (NP1) and neuropilin-2 (NP2) are receptors for semaphorins, which act as axonal chemorepellents, and for members of the vascular endothelial growth factor (VEGF) family of angiogenic growth factors. The NP1 and NP2 genes consist of 17 exons, and protein isoforms are expressed because of alternative transcript splicing. Here we report the identification of a new NP1 transcript (designated NRP1(Delta exon16)) that contains an arginine codon in place of exon 16-derived sequences at a locus between the c-domain and membrane spanning domain. NRP1(Delta exon16) is expressed in endothelial cells, astrocytes, and various tumor cell lines, and accounts for 30% of the total NRP1 transcript. After cellular expression of NRP1(Delta exon16), we found (unlike the two previously identified alternatively spliced NRP1 isoforms) no evidence that the extracellular domain of NRP1(Delta exon16) is secreted from cells as a soluble protein. (125)I-VEGF bound with high affinity to NRP1 and NRP1(Delta exon16) expressing cells, and VEGF treatment led to the formation of complexes between VEGFR-2 and either NRP1 or NRP1(Delta exon16). It is concluded that NRP1 and NRP1(Delta exon16) mediate VEGF-induced signaling in a similar manner.
神经纤毛蛋白-1（NP1）和神经纤毛蛋白-2（NP2）是信号素的受体，信号素作为轴突化学排斥因子起作用，同时它们也是血管内皮生长因子（VEGF）家族血管生成生长因子成员的受体。NP1和NP2基因由17个外显子组成，由于转录剪接的选择性，会表达出不同的蛋白质异构体。在此，我们报告鉴定出一种新的NP1转录本（命名为NRP1(Δ外显子16)），该转录本在c结构域和跨膜结构域之间的位点包含一个精氨酸密码子，取代了源自外显子16的序列。NRP1(Δ外显子16)在内皮细胞、星形胶质细胞和各种肿瘤细胞系中表达，占总NRP1转录本的30%。在细胞中表达NRP1(Δ外显子16)后，我们发现（与之前鉴定的两种选择性剪接的NRP1异构体不同），没有证据表明NRP1(Δ外显子16)的细胞外结构域作为可溶性蛋白从细胞中分泌出来。（125）I-VEGF以高亲和力与表达NRP1和NRP1(Δ外显子16)的细胞结合，VEGF处理导致VEGFR-2与NRP1或NRP1(Δ外显子16)之间形成复合物。得出的结论是，NRP1和NRP1(Δ外显子16)以类似的方式介导VEGF诱导的信号传导。
