Neuropilin 2

Neuropilin 2 (NRP2) is a protein that in humans is encoded by the NRP2 gene. It is a member of the neuropilin family and plays a crucial role in the development of the cardiovascular and nervous systems, as well as in the regulation of angiogenesis and lymphangiogenesis. Neuropilin 2 acts as a receptor for both class 3 semaphorins and members of the vascular endothelial growth factor (VEGF) family, mediating cellular responses to these guidance cues in both physiological and pathological processes.

Structure

Neuropilin 2 is a type I transmembrane protein characterized by a large extracellular domain, a single transmembrane domain, and a short cytoplasmic domain. The extracellular domain contains two CUB domains, two F5/8 type C domains, and a MAM domain, which are involved in ligand binding and dimerization. The cytoplasmic domain, although short, is critical for the intracellular signaling pathways initiated upon ligand binding.

Function

The primary function of neuropilin 2 is to serve as a co-receptor for class 3 semaphorins (sema3) and members of the VEGF family. In the nervous system, NRP2, in conjunction with plexins, mediates the repulsive guidance cues necessary for axon guidance and neuronal migration. In the vascular system, it is involved in angiogenesis, the process of new blood vessel formation, by modulating the response of endothelial cells to VEGF. Additionally, NRP2 plays a role in lymphangiogenesis, the formation of lymphatic vessels, which is essential for maintaining fluid homeostasis and for immune responses.

Clinical Significance

Alterations in the expression or function of neuropilin 2 have been implicated in various pathological conditions, including cancer, cardiovascular diseases, and neurological disorders. In cancer, overexpression of NRP2 has been observed in several types of tumors, where it is associated with increased tumor growth, metastasis, and poor prognosis. This is partly due to its role in enhancing angiogenesis and lymphangiogenesis, providing the tumor with nutrients and pathways for dissemination. In cardiovascular diseases, dysregulation of NRP2-mediated signaling pathways can contribute to the development of atherosclerosis and other vascular abnormalities. In the nervous system, aberrant NRP2 signaling has been linked to neurodevelopmental disorders and neuropathic pain.

Research Directions

Current research on neuropilin 2 is focused on elucidating its complex signaling pathways and interactions with other molecules, with the aim of developing targeted therapies for diseases associated with NRP2 dysregulation. Inhibitors of NRP2 and its ligands are being explored as potential therapeutic agents in cancer, cardiovascular diseases, and other conditions where NRP2 plays a pathological role.

See Also

• Neuropilin 1
• Semaphorin
• Vascular endothelial growth factor
• Angiogenesis
• Lymphangiogenesis