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Neuropilin

Protein receptor active in neurons

Field	Value
Symbol	NRP
Name	Neuropilin
image	Neuropilin.png
caption	Crystallographic structure of the dimeric B1 domain of human neuropilin 1.
Pfam	PF11980
InterPro	IPR014648
Membranome superfamily	16

Neuropilin is a protein receptor active in neurons.

There are two forms of Neuropilins, NRP-1 and NRP-2. Neuropilins are transmembrane glycoproteins, first documented to regulate neurogenesis and angiogenesis by complexing with Plexin receptors/class-3 semaphorin ligands and Vascular Endothelial Growth Factor (VEGF) receptors/VEGF ligands, respectively. Neuropilins predominantly act as co-receptors as they have a very small cytoplasmic domain and thus rely upon other cell surface receptors to transduce their signals across a cell membrane. Recent studies have shown that Neuropilins are multifunctional and can partner with a wide variety of transmembrane receptors. Neuropilins are therefore associated with numerous signalling pathways including those activated by Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Hepatocyte Growth Factor (HGF), Insulin-like Growth Factor (IGF), Platelet Derived Growth Factor (PDGF) and Transforming Growth Factor beta (TGFβ). Although Neuropilins are commonly found at the cell surface, they have also been reported within the mitochondria and nucleus. Both Neuropilin family members can also be found in soluble forms created by alternative splicing or by ectodomain shedding from the cell surface.

The pleiotropic nature of the NRP receptors results in their involvement in cellular processes, such as axon guidance and angiogenesis, the immune response and remyelination. Therefore, dysregulation of NRP activity has been implicated in many pathological conditions, including many types of cancer and cardiovascular disease.

Applications

Neuropilin-1 is a therapeutic target protein in the treatment for leukemia and lymphoma, since It has been shown that there is increased expression in neuropilin-1 in leukemia and lymphoma cell lines. Also, antagonism of neuropilin-1 has been found to inhibit tumour cell migration and adhesion.

Structure

Neuropilins contain the following four domains:

N-terminal CUB domain (for complement C1r/C1s, Uegf, Bmp1)
Coagulation factor 5/8 type, C-terminal (discoidin domain)
MAM domain (for meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu)
C-terminal neuropilin

The structure of B1 domain (coagulation factor 5/8 type) of neuropilin-1 was determined through X-Ray Diffraction with a resolution of 2.90 Å. The secondary structure of this domain is 5% alpha helical and 46% beta sheet.

References

(March 2010). "Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction". Journal of Medicinal Chemistry.
(April 2008). "Neuropilins: structure, function and role in disease". The Biochemical Journal.
(January 2010). "Neuropilin, you gotta let me know: should I stay or should I go?". Cell Adhesion & Migration.
(May 2016). "The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature". Current Opinion in Hematology.
(2017). "Proteases in Human Diseases". Springer Singapore.
(January 2019). "Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress". iScience.
(August 2018). "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.
(December 2000). "Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms". Genomics.
(August 2016). "Polysialylation and lipopolysaccharide-induced shedding of E-selectin ligand-1 and neuropilin-2 by microglia and THP-1 macrophages". Glia.
(2014). "A perspective on the role of class III semaphorin signaling in central nervous system trauma". Frontiers in Cellular Neuroscience.
(February 2019). "Neuropilins in the Context of Tumor Vasculature". International Journal of Molecular Sciences.
(May 2016). "The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature". Current Opinion in Hematology.
(November 2015). "Neuropilins 1 and 2 mediate neointimal hyperplasia and re-endothelialization following arterial injury". Oxford University Press.
(2020-07-21). "Emerging Roles for Neuropilin-2 in Cardiovascular Disease". International Journal of Molecular Sciences.
(January 2011). "Targeting neuropilin-1 in human leukemia and lymphoma". Blood.
(February 2010). "Neuropilin-1 antagonism in human carcinoma cells inhibits migration and enhances chemosensitivity". British Journal of Cancer.

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This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page.

transmembrane-receptors single-pass-transmembrane-proteins

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