Neuropilin

{{Short description|Protein receptor active in neurons}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox protein family

| Symbol = NRP

| Name = Neuropilin

| image = Neuropilin.png

| width =

| caption = Crystallographic structure of the dimeric B1 domain of human neuropilin 1.{{PDB|3I97}}; {{cite journal | vauthors = Jarvis A, Allerston CK, Jia H, Herzog B, Garza-Garcia A, Winfield N, Ellard K, Aqil R, Lynch R, Chapman C, Hartzoulakis B, Nally J, Stewart M, Cheng L, Menon M, Tickner M, Djordjevic S, Driscoll PC, Zachary I, Selwood DL | title = Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction | journal = Journal of Medicinal Chemistry | volume = 53 | issue = 5 | pages = 2215–26 | date = March 2010 | pmid = 20151671 | pmc = 2841442 | doi = 10.1021/jm901755g }}

| Pfam= PF11980

| InterPro= IPR014648

| SMART=

| Prosite =

| SCOP =

| TCDB =

| OPM family=

| OPM protein=

| PDB=

| Membranome superfamily = 16

}}

{{infobox protein

| Name = neuropilin 1

| caption =

| image =

| width =

| HGNCid = 8004

| Symbol = NRP1

| AltSymbols =

| EntrezGene = 8829

| OMIM = 602069

| RefSeq = NM_001024628

| UniProt = O14786

| PDB = 3I97

| ECnumber =

| Chromosome = 10

| Arm = p

| Band = 12

| LocusSupplementaryData =

}}

{{infobox protein

| Name = neuropilin 2

| caption =

| image =

| width =

| HGNCid = 8005

| Symbol = NRP2

| AltSymbols =

| EntrezGene = 8828

| OMIM = 602070

| RefSeq = NM_201279

| UniProt = O60462

| PDB =

| ECnumber =

| Chromosome = 2

| Arm = q

| Band = 34

| LocusSupplementaryData =

}}

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.{{cite journal | vauthors = Pellet-Many C, Frankel P, Jia H, Zachary I | title = Neuropilins: structure, function and role in disease | journal = The Biochemical Journal | volume = 411 | issue = 2 | pages = 211–26 | date = April 2008 | pmid = 18363553 | doi = 10.1042/bj20071639 }}{{cite journal | vauthors = Schwarz Q, Ruhrberg C | title = Neuropilin, you gotta let me know: should I stay or should I go? | journal = Cell Adhesion & Migration | volume = 4 | issue = 1 | pages = 61–6 | date = January 2010 | pmid = 20026901 | doi = 10.4161/cam.4.1.10207 | pmc = 2852559 }} 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).{{cite journal | vauthors = Kofler N, Simons M | title = The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature | journal = Current Opinion in Hematology | volume = 23 | issue = 3 | pages = 260–7 | date = May 2016 | pmid = 26849476 | doi = 10.1097/moh.0000000000000233 | pmc = 4957701 }}{{cite book | vauthors = Roy S, Pramanik A, Chakraborti T, Chakraborti S |chapter=Multifaceted Role of Matrix Metalloproteases on Human Diseases |title=Proteases in Human Diseases|date=2017|pages=21–40|publisher=Springer Singapore|isbn=978-981-10-3161-8 |doi=10.1007/978-981-10-3162-5_2}} Although Neuropilins are commonly found at the cell surface, they have also been reported within the mitochondria and nucleus.{{cite journal | vauthors = Issitt T, Bosseboeuf E, De Winter N, Dufton N, Gestri G, Senatore V, Chikh A, Randi AM, Raimondi C | title = Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress | journal = iScience | volume = 11 | pages = 205–223 | date = January 2019 | pmid = 30623799 | pmc = 6327076 | doi = 10.1016/j.isci.2018.12.005 | bibcode = 2019iSci...11..205I }}{{cite journal | vauthors = Mehta V, Fields L, Evans IM, Yamaji M, Pellet-Many C, Jones T, Mahmoud M, Zachary I | title = 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 | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 38 | issue = 8 | pages = 1845–1858 | date = August 2018 | pmid = 29880492 | pmc = 6092111 | doi = 10.1161/ATVBAHA.118.311118 }} Both Neuropilin family members can also be found in soluble forms created by alternative splicing or by ectodomain shedding from the cell surface.{{cite journal | vauthors = Rossignol M, Gagnon ML, Klagsbrun M | title = Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms | journal = Genomics | volume = 70 | issue = 2 | pages = 211–22 | date = December 2000 | pmid = 11112349 | doi = 10.1006/geno.2000.6381 }}{{cite journal | vauthors = Werneburg S, Buettner FF, Erben L, Mathews M, Neumann H, Mühlenhoff M, Hildebrandt H | title = Polysialylation and lipopolysaccharide-induced shedding of E-selectin ligand-1 and neuropilin-2 by microglia and THP-1 macrophages | journal = Glia | volume = 64 | issue = 8 | pages = 1314–30 | date = August 2016 | pmid = 27159043 | doi = 10.1002/glia.23004 | s2cid = 3713077 }}

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.{{cite journal | vauthors = Mecollari V, Nieuwenhuis B, Verhaagen J | title = A perspective on the role of class III semaphorin signaling in central nervous system trauma | journal = Frontiers in Cellular Neuroscience | volume = 8 | pages = 328 | date = 2014 | pmid = 25386118 | pmc = 4209881 | doi = 10.3389/fncel.2014.00328 | doi-access = free }} Therefore, dysregulation of NRP activity has been implicated in many pathological conditions, including many types of cancer and cardiovascular disease.{{cite journal | vauthors = Niland S, Eble JA | title = Neuropilins in the Context of Tumor Vasculature | journal = International Journal of Molecular Sciences | volume = 20 | issue = 3 | pages = 639 | date = February 2019 | pmid = 30717262 | pmc = 6387129 | doi = 10.3390/ijms20030639 | doi-access = free }}{{cite journal | vauthors = Kofler N, Simons M | title = The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature | journal = Current Opinion in Hematology | volume = 23 | issue = 3 | pages = 260–7 | date = May 2016 | pmid = 26849476 | pmc = 4957701 | doi = 10.1097/MOH.0000000000000233 }}{{cite journal | vauthors = Pellet-Many C, Mehta V, Fields L, Mahmoud M, Lowe V, Evans I, Ruivo J, Zachary I | title = Neuropilins 1 and 2 mediate neointimal hyperplasia and re-endothelialization following arterial injury | journal = Cardiovascular Research | volume = 108 | issue = 2 | pages = 288–98 | date = November 2015 | pmid = 26410366 | pmc = 4614691 | doi = 10.1093/cvr/cvv229 | publisher = Oxford University Press | oclc = 927518632 }}{{Cite journal|last1=Harman|first1=Jennifer L.|last2=Sayers|first2=Jacob|last3=Chapman|first3=Chey|last4=Pellet-Many|first4=Caroline |date=2020-07-21|title=Emerging Roles for Neuropilin-2 in Cardiovascular Disease|journal=International Journal of Molecular Sciences|language=en|volume=21|issue=14|pages=5154|doi=10.3390/ijms21145154 |pmid=32708258|pmc=7404143|doi-access=free}}