|Detection of Neuropilin‑1 in HUVEC Human Cells by Flow Cytometry. HUVEC human umbilical vein endothelial cells were stained with Mouse Anti-Human Neuropilin-1 Alexa Fluor® 700-conjugated Monoclonal Antibody (Catalog # FAB3870N, filled histogram) or isotype control antibody (Catalog # IC003N, open histogram). View our protocol for Staining Membrane-associated Proteins.|
Neuropilin-1 (Npn-1, previously neuropilin; also CD304) 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) human Npn‑1 contains a 623 aa extracellular domain (ECD) that shows 92‑95% aa identity with mouse, rat, 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). C-terminally divergent splice variants with 704, 644, 609, and 551 aa lack the MAM and TM domains and are demonstrated or presumed to be soluble antagonists (1, 5‑7). A 906 aa form lacks a TM segment, but secretion has not been found (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 arteries during development or those undergoing remodeling (1, 2). Npn-1 is also expressed on dendritic cells and mediates DC-induced T cell proliferation (13).
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