Characterization of a new alternatively spliced neuropilin-1 isoform.
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.
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D042783:Endothelial Cells / Q000378:metabolism*; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D039942:Neuropilin-1 / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1