Neuropeptide S receptor

The neuropeptide S receptor (NPSR) is a member of the G-protein coupled receptor superfamily of integral membrane proteins[5] which binds neuropeptide S (NPS).[6] It was formerly an orphan receptor, GPR154, until the discovery of neuropeptide S as the endogenous ligand. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. This gene is a member of the G protein-coupled receptor 1 family and encodes a plasma membrane protein. Mutations in this gene have also been associated with this disease.[7]

NPSR1
Identifiers
AliasesNPSR1, ASRT2, GPR154, GPRA, NPSR, PGR14, VRR1, neuropeptide S receptor 1
External IDsOMIM: 608595 MGI: 2441738 HomoloGene: 45515 GeneCards: NPSR1
Orthologs
SpeciesHumanMouse
Entrez

387129

319239

Ensembl

ENSG00000187258

ENSMUSG00000043659

UniProt

Q6W5P4

Q8BZP8

RefSeq (mRNA)

NM_207173
NM_001300933
NM_001300934
NM_001300935
NM_207172

NM_175678

RefSeq (protein)

NP_001287862
NP_001287863
NP_001287864
NP_997055
NP_997056

NP_783609

Location (UCSC)Chr 7: 34.66 – 34.88 MbChr 9: 24.01 – 24.23 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Clinical significance

In the CNS, activation of the NPSR by NPS promotes arousal and anxiolytic-like effects.[8][9]

In addition, mututations in NPSR have been linked to a susceptibility to asthma (rs3249801, A107I).[10] Hence NPSR has also been called GPRA (G protein-coupled receptor for asthma susceptibility). Activation of NPSR in the airway epithelium has a number of effects including upregulation of matrix metalloproteinases which are involved in the pathogenesis of asthma.[11] It has been shown that activation of NPSR by NPS affects both gastrointestinal motility and mucosal permeability simultaneously. Aberrant signaling and upregulation of NPSR1 could potentially exacerbate dysmotility and hyperpermeability by local mechanisms in gastrointestinal functional and inflammatory reactions.[12]

The very rare NPSR mutation Y206H, which makes the receptor more sensitive to NPS, is found in human families that need less sleep time than normal ones. It has similar effects in transgenic mice, making them resistant to memory impairment caused by lack of sleep.[13]

References
  1. GRCh38: Ensembl release 89: ENSG00000187258 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000043659 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, Brown A, Rodriguez SS, Weller JR, Wright AC, Bergmann JE, Gaitanaris GA (Apr 2003). "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America. 100 (8): 4903–8. Bibcode:2003PNAS..100.4903V. doi:10.1073/pnas.0230374100. PMC 153653. PMID 12679517.
  6. Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Räisänen-Sokolowski A, Laitinen A, Laitinen LA, Kere J, Laitinen T (Sep 2005). "Characterization of GPRA, a novel G protein-coupled receptor related to asthma". American Journal of Respiratory Cell and Molecular Biology. 33 (3): 262–70. doi:10.1165/rcmb.2004-0405OC. PMID 15947423.
  7. "Entrez Gene: NPSR1 neuropeptide S receptor 1".
  8. Xu YL, Reinscheid RK, Huitron-Resendiz S, Clark SD, Wang Z, Lin SH, Brucher FA, Zeng J, Ly NK, Henriksen SJ, de Lecea L, Civelli O (Aug 2004). "Neuropeptide S: a neuropeptide promoting arousal and anxiolytic-like effects". Neuron. 43 (4): 487–97. doi:10.1016/j.neuron.2004.08.005. PMID 15312648. S2CID 15601843.
  9. Okamura N, Reinscheid RK (Aug 2007). "Neuropeptide S: a novel modulator of stress and arousal". Stress. 10 (3): 221–6. doi:10.1080/10253890701248673. PMID 17613937. S2CID 39068808.
  10. Laitinen T, Polvi A, Rydman P, Vendelin J, Pulkkinen V, Salmikangas P, Mäkelä S, Rehn M, Pirskanen A, Rautanen A, Zucchelli M, Gullstén H, Leino M, Alenius H, Petäys T, Haahtela T, Laitinen A, Laprise C, Hudson TJ, Laitinen LA, Kere J (Apr 2004). "Characterization of a common susceptibility locus for asthma-related traits". Science. 304 (5668): 300–4. Bibcode:2004Sci...304..300L. doi:10.1126/science.1090010. PMID 15073379. S2CID 9149671.
  11. Vendelin J, Bruce S, Holopainen P, Pulkkinen V, Rytilä P, Pirskanen A, Rehn M, Laitinen T, Laitinen LA, Haahtela T, Saarialho-Kere U, Laitinen A, Kere J (Oct 2006). "Downstream target genes of the neuropeptide S-NPSR1 pathway". Human Molecular Genetics. 15 (19): 2923–35. doi:10.1093/hmg/ddl234. PMID 16926187.
  12. Wan Saudi WS, Halim MA, Rudholm-Feldreich T, Gillberg L, Rosenqvist E, Tengholm A, Sundbom M, Karlbom U, Näslund E, Webb DL, Sjöblom M, Hellström PM (Oct 2015). "Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide". Am J Physiol Gastrointest Liver Physiol. 309 (9): G625-34. doi:10.1152/ajpgi.00104.2015. PMID 26206857.
  13. Xing L, Shi G, Mostovoy Y, Gentry NW, Fan Z, McMahon TB, et al. (16 October 2019). "Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation" (PDF). Science Translational Medicine. 11 (514): eaax2014. doi:10.1126/scitranslmed.aax2014. PMC 7587149. PMID 31619542. S2CID 204756335.

Further reading

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