Recombinant Mouse Neuropilin-1 Protein, CF

Neuropilin-1 (Npn-1, previously neuropilin; also CD304 or BDCA4 in humans) is a 130‑140 kDa type I transmembrane (TM) glycoprotein that regulates axon guidance and angiogenesis (1‑4). The full-length 923 amino acid (aa) mouse Npn-1 contains a 623 aa extracellular domain (ECD) that shares 98% aa identity with rat and 93% aa identity with human, equine, bovine and canine Npn-1 (3, 4). The ECD contains two N-terminal CUB domains (termed a1a2), two domains with homology to coagulation factors V and VIII (b1b2) and a MAM (meprin) domain (c). At least one splice variant that diverges at aa 587 and lacks the TM domain has been sequenced (5). This form is potentially a soluble antagonist, based on results from human Npn-1 splice variants (1, 6‑8). The sema domains of Class III secreted semaphorins such as Sema3A bind Npn-1 a1a2 (9). Heparin, the heparin-binding forms of VEGF (VEGF₁₆₅, VEGF-B and VEGF-E), PlGF (PlGF2), and the C‑terminus of Sema3 bind the b1b2 region (9, 10). Npn-1 and Npn-2 share 48% aa identity within the ECD and can form homo- and hetero-oligomers via interaction of their MAM domains (1). Neuropilins show partially overlapping expression in neuronal and endothelial cells during development (1, 2). Both Neuropilins act as co-receptors with plexins, mainly plexin A3 and A4, to bind class III semaphorins that mediate axon repulsion (11). However, only Npn-1 binds Sema3A, and only Npn-2 binds Sema3F (1). Both are co‑receptors with VEGF R2 (also called KDR or Flk-1) for VEGF₁₆₅ binding (1). Sema3A signaling can be blocked by VEGF₁₆₅, which has higher affinity for Npn-1 (12). Npn-1 is preferentially expressed in developing or remodeling arteries (1, 2). Npn-1 is also expressed on dendritic cells and mediates DC-induced T cell proliferation (13).