Neuropilin Explained

Symbol:NRP
Neuropilin
Pfam:PF11980
Interpro:IPR014648
Membranome Superfamily:16
neuropilin 1
Hgncid:8004
Symbol:NRP1
Entrezgene:8829
Omim:602069
Refseq:NM_001024628
Uniprot:O14786
Pdb:3I97
Chromosome:10
Arm:p
Band:12
neuropilin 2
Hgncid:8005
Symbol:NRP2
Entrezgene:8828
Omim:602070
Refseq:NM_201279
Uniprot:O60462
Chromosome:2
Arm:q
Band:34

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.[1] [2] 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).[3] [4] Although Neuropilins are commonly found at the cell surface, they have also been reported within the mitochondria and nucleus.[5] [6] Both Neuropilin family members can also be found in soluble forms created by alternative splicing or by ectodomain shedding from the cell surface.[7] [8]

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.[9] Therefore, dysregulation of NRP activity has been implicated in many pathological conditions, including many types of cancer and cardiovascular disease.[10] [11] [12] [13]

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.[14] Also, antagonism of neuropilin-1 has been found to inhibit tumour cell migration and adhesion.[15]

Structure

Neuropilins contain the following four domains:

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.

Notes and References

  1. Pellet-Many C, Frankel P, Jia H, Zachary I . Neuropilins: structure, function and role in disease . The Biochemical Journal . 411 . 2 . 211–26 . April 2008 . 18363553 . 10.1042/bj20071639 .
  2. Schwarz Q, Ruhrberg C . Neuropilin, you gotta let me know: should I stay or should I go? . Cell Adhesion & Migration . 4 . 1 . 61–6 . January 2010 . 20026901 . 10.4161/cam.4.1.10207 . 2852559 .
  3. Kofler N, Simons M . The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature . Current Opinion in Hematology . 23 . 3 . 260–7 . May 2016 . 26849476 . 10.1097/moh.0000000000000233 . 4957701 .
  4. Book: Roy S, Pramanik A, Chakraborti T, Chakraborti S . Multifaceted Role of Matrix Metalloproteases on Human Diseases . Proteases in Human Diseases. 2017. 21–40. Springer Singapore. 978-981-10-3161-8 . 10.1007/978-981-10-3162-5_2.
  5. Issitt T, Bosseboeuf E, De Winter N, Dufton N, Gestri G, Senatore V, Chikh A, Randi AM, Raimondi C . Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress . iScience . 11 . 205–223 . January 2019 . 30623799 . 6327076 . 10.1016/j.isci.2018.12.005 . 2019iSci...11..205I .
  6. Mehta V, Fields L, Evans IM, Yamaji M, Pellet-Many C, Jones T, Mahmoud M, Zachary I . 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 . 38 . 8 . 1845–1858 . August 2018 . 29880492 . 6092111 . 10.1161/ATVBAHA.118.311118 .
  7. Rossignol M, Gagnon ML, Klagsbrun M . Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms . Genomics . 70 . 2 . 211–22 . December 2000 . 11112349 . 10.1006/geno.2000.6381 .
  8. Werneburg S, Buettner FF, Erben L, Mathews M, Neumann H, Mühlenhoff M, Hildebrandt H . Polysialylation and lipopolysaccharide-induced shedding of E-selectin ligand-1 and neuropilin-2 by microglia and THP-1 macrophages . Glia . 64 . 8 . 1314–30 . August 2016 . 27159043 . 10.1002/glia.23004 . 3713077 .
  9. Mecollari V, Nieuwenhuis B, Verhaagen J . A perspective on the role of class III semaphorin signaling in central nervous system trauma . Frontiers in Cellular Neuroscience . 8 . 328 . 2014 . 25386118 . 4209881 . 10.3389/fncel.2014.00328 . free .
  10. Niland S, Eble JA . Neuropilins in the Context of Tumor Vasculature . International Journal of Molecular Sciences . 20 . 3 . 639 . February 2019 . 30717262 . 6387129 . 10.3390/ijms20030639 . free .
  11. Kofler N, Simons M . The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature . Current Opinion in Hematology . 23 . 3 . 260–7 . May 2016 . 26849476 . 4957701 . 10.1097/MOH.0000000000000233 .
  12. Pellet-Many C, Mehta V, Fields L, Mahmoud M, Lowe V, Evans I, Ruivo J, Zachary I . Neuropilins 1 and 2 mediate neointimal hyperplasia and re-endothelialization following arterial injury . Cardiovascular Research . 108 . 2 . 288–98 . November 2015 . 26410366 . 4614691 . 10.1093/cvr/cvv229 . Oxford University Press . 927518632 .
  13. Harman. Jennifer L.. Sayers. Jacob. Chapman. Chey. Pellet-Many. Caroline . 2020-07-21. Emerging Roles for Neuropilin-2 in Cardiovascular Disease. International Journal of Molecular Sciences. en. 21. 14. 5154. 10.3390/ijms21145154 . 32708258. 7404143. free.
  14. Karjalainen K, Jaalouk DE, Bueso-Ramos CE, Zurita AJ, Kuniyasu A, Eckhardt BL, Marini FC, Lichtiger B, O'Brien S, Kantarjian HM, Cortes JE, Koivunen E, Arap W, Pasqualini R . Targeting neuropilin-1 in human leukemia and lymphoma . Blood . 117 . 3 . 920–7 . January 2011 . 21063027 . 3298438 . 10.1182/blood-2010-05-282921 .
  15. Jia H, Cheng L, Tickner M, Bagherzadeh A, Selwood D, Zachary I . Neuropilin-1 antagonism in human carcinoma cells inhibits migration and enhances chemosensitivity . British Journal of Cancer . 102 . 3 . 541–52 . February 2010 . 20087344 . 2822953 . 10.1038/sj.bjc.6605539 .

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