Neuropilin is a non-tyrosine kinase transmembrane glycoprotein, including two members, NRP-1 and NRP-2, of which NRP-1 is the first discovered NRP family protein. Neuropilin is a receptor for a variety of biological molecules and ligands, including type I and III Sema molecules and vascular endothelial growth factor (VEGF). Neuropilin participates in a variety of physiological activities, mainly the following:
- NRP-1: NRP-1 is mainly involved in axon guidance, angiogenesis, high expression on regulatory T cells, cardiac development and immune regulation.
- NRP-2: NRP-2 participates in lymphangiogenesis, supports axon structure and vascular development and other processes.
Neuropilin holds significant potential for application in the treatment of diseases related to the development of the mammalian nervous system, as well as in tumor therapy.
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The Structure of Neuropilin
NRP1 is the first discovered Nrp proteins. The functions and effects of neuropilin overlap to make a structurally integrated network to transmit nerve signals quickly and efficiently. Neuropilin has been involved in hand-free protrusions and networks. Foxp3 is a potent surface marker for Treg.
Nrp1 is composed of 3 domains, extracellular domain, transmembrane domain, and intracellular domain. These basic structures are 44, 15, and 15 percent identical among Nrp2A, Nrp2B, and Nrp1. The extracellular domain of one of them is larger and consists of three domains: CUB (a1/a2), FV/FVIII (b1/b2), and MAM (c). It's short and it can't handle intracellular signaling on its own. It must heterodimerize with other membrane receptors for Nrp1 downstream signal transduction.
Physiological and Pathological Effects of Neuropilin
Neuropilin is a single transmembrane receptor that can bind multiple biological molecules and ligands such as vascular endothelial growth factor (VEGF), three types of signaling proteins (SEMA3A and SEMA3F) and transforming growth factor-β (TGF-β). When attached to different biological molecules, neuropilin works differently. NRP-1, for instance, works with transforming growth factor- (TGF-β) to modulate cell migration matrix production and more. NRP-1 and NRP-2 can even overlap to bind, for example, to three signaling proteins that might be involved in axon guidance and neuronal growth.
Fig. 1 Neuropilin (NRP1) and vascular endothelial growth factor (VEGF) interaction (Mehta, V.; et al. 2018).
Related Diseases
NRP 1 and NRP2 are the same thing, transmembrane receptors that promote neuronal regulation and angiogenesis. NRP1 is a transmembrane glycoprotein that is a receptor for many extracellular ligands, including class III/IV semaphorins, some isoforms of vascular endothelial growth factor and transforming growth factor-beta. NRPs belong to class 3 semaphorin (orientational regulators of neurons) and vascular endothelial growth factor (VEGF) angiogenic factor families.
- Polycystic kidney disease
- Retinoblastoma
- Laryngeal dysgenesis syndrome
- Marfan syndrome
- Airway ciliary dysfunction
- Breast cancer
- Lung cancer
Conclusion
Neuropilin plays a fundamental role in regulating neuronal development, synaptic transmission, and overall neuronal function. Neuropilin is often used for ligand binding, receptor characterization, and functional testing, and can be used for drug screening and drug discovery. Neuropilins play an important role in the nervous system. They help maintain the shape of neurons, support the structure of axons, and promote the conduction of nerve signals. Currently, researchers are working to use neuropilin for targeted disease treatment, which has important implications for clinical research.
References
- Chuckran, C., et al. Neuropilin-1: a checkpoint target with unique implications for cancer immunology and immunotherapy. Journal for immunotherapy of cancer 2020, 8(2): 1-8.
- Mayi, B., et al. The role of Neuropilin-1 in COVID-19. PLoS pathogens. 2021, 17(1): e1009153.
- Mehta, V., et al. VEGF (vascular endothelial growth factor) induces NRP1 (neuropilin-1) cleavage via ADAMs (a disintegrin and metalloproteinase) 9 and 10 to generate novel carboxy-terminal NRP1 fragments that regulate angiogenic signaling. Arteriosclerosis, thrombosis, and vascular biology. 2018, 38(8): 1845-1858.
- Wang, S., et al. Neuropilin-1, a myeloid cell-specific protein, is an inhibitor of HIV-1 infectivity. Proceedings of the National Academy of Sciences. 2022, 119(2): e2114884119.
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