Neuropilin-Plexin A receptor complex (NRP-PLXNA complex)

The Neuropilin-Plexin A receptor complex is a heteromeric cell-surface signaling unit composed of Neuropilin-1 (NRP1) or Neuropilin-2 (NRP2) and members of the Plexin A family (PLXNA1, PLXNA2, PLXNA3, or PLXNA4) (Takahashi et al., 1999, PMID: 10520994). This complex serves as the primary receptor for Class 3 Semaphorins (SEMA3), where the Neuropilin subunit acts as the high-affinity ligand-binding component and the Plexin A subunit functions as the signal transducer via its intracellular GTPase-activating protein (GAP) domain (UniProt P35368). Beyond its fundamental role in axonal guidance and neuronal development, the complex is a critical regulator of angiogenesis and vascular permeability, often acting as a co-receptor for Vascular Endothelial Growth Factor (VEGF) (Grandclement & Pallandre, 2011, PMID: 22438566). In oncology, overexpression of the NRP-Plexin A complex is associated with tumor progression, increased metastatic potential, and resistance to anti-angiogenic therapies (PubMed, PMID: 22438566). Therapeutic strategies targeting this complex include monoclonal antibodies, such as vesencumab (MNRP1685A), and small molecules designed to inhibit the protein-protein interactions or ligand-binding sites essential for downstream signaling (NCI Drug Dictionary).

Other names

NRP/Plexin complexSemaphorin 3 receptor complexNeuropilin-Plexin A1-4 complexNRP1-PLXNA complexNRP2-PLXNA complex

Inhibition of ligand binding to Neuropilin subunits and disruption of Neuropilin-Plexin complex dimerization to block Semaphorin and VEGF signaling.