Biology:GPR173

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Short description: Protein-coding gene in humans

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Probable G-protein coupled receptor 173 is a protein that in humans is encoded by the GPR173 gene.[1][2]

Function

GPR173 (Also known as Super-Conserved Receptor Expressed in Brain 3, or SREB3) is a highly conserved G protein-coupled receptor (GPCR) that plays a significant role in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis, which is central to reproductive function.[3][4][5] It is expressed in the brain and ovaries, where it is considered the putative receptor for the peptide hormone phoenixin (PNX).

Activation of GPR173 by phoenixin potentiates the secretion of luteinizing hormone (LH) in response to gonadotropin-releasing hormone (GnRH), thereby promoting ovarian cycling and supporting reproductive processes.[4][5] Beyond reproduction, GPR173 has been implicated in diverse physiological functions such as food intake regulation, learning and memory, anxiety, inflammatory responses, and cardiac protection, largely through its modulation by phoenixin.[5]

Additionally, GPR173 may act as a receptor for cholecystokinin (CCK) in certain brain regions, mediating inhibitory synaptic plasticity and potentially serving as a therapeutic target for disorders involving excitation-inhibition imbalance.[6] The expression of GPR173 can be influenced by nutritional and environmental factors, indicating its role as a sensor and mediator in integrating external signals with neuroendocrine pathways.[3]

Ligands

GPR173 is an orphan class GPCR, however recent work has identified several compounds that may function as endogenous ligands.

Phoenixin

Recent studies have found GPR173 may act as a receptor for the peptides phoenixin-14 (PNX-14) and phoenixin-20 (PNX-20).[7][8][4] Both Phoenixins are alternate cleavage products of SMIM20.[7] PNX-20 treatments increased CREB phosphylation (pCREB) [9][10][11][12] and ERK1/2 phosphorylation (pERK1/2)[10] in various cell lines. These effects of PNX-20 were found to be dependent on GPR173 expression.[10] PNX-14 treatments were found to increase intracellular cAMP treatments under specific conditions within adipocytes.[13] As a ligand for GPR173, PNX-20 was found to have self regulatory behaviors by increasing GPR173 expression.[12][11]

GnRH-(1-5)

GnRH-(1-5) is a degradation product of GnRH. GnRH-(1-5) was found to induce STAT3 phosphorylation (pSTAT3) in GN11 cells.[14] GnRH-(1-5) was not found to affect cAMP levels or IP1 levels in GN11 cells, and did not recruit Gα12 or Gα13 to GPR173.[15] Activation of a G subunit associated pathway could not be confirmed, however GnRH-(1-5) treatments did have GPR173 recruit β-Arrestin 2 and PTEN.[15] GnRH-(1-5) induced production of pSTAT3 via GPR173 was found to be dependent on PTEN activity.[15]

Cholecystokinin 8 (CCK8)

CCK8 has been found to interact with GPR173 in cell surface binding assays utilizing Flag-Tag assays.[6] CCK1R and CCK2R are established receptors for CCk8 that signal through Gαq/11. In GPR173+/+ CHO cells, CCK8 was found to mobilize [Ca2+]i with similar EC50 compared to CCK1R and CCK2R.[6]

See also

References

  1. ↑ "An evolutionarily conserved G-protein coupled receptor family, SREB, expressed in the central nervous system". Biochemical and Biophysical Research Communications 272 (2): 576–582. Jul 2000. doi:10.1006/bbrc.2000.2829. PMID 10833454. Bibcode: 2000BBRC..272..576M. 
  2. ↑ "Entrez Gene: GPR173 G protein-coupled receptor 173". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=54328. 
  3. ↑ 3.0 3.1 "Regulation of Gpr173 expression, a putative phoenixin receptor, by saturated fatty acid palmitate and endocrine-disrupting chemical bisphenol A through a p38-mediated mechanism in immortalized hypothalamic neurons". Molecular and Cellular Endocrinology 485: 54–60. April 2019. doi:10.1016/j.mce.2019.01.026. PMID 30716364. 
  4. ↑ 4.0 4.1 4.2 "Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 311 (3): R489–R496. September 2016. doi:10.1152/ajpregu.00191.2016. ISSN 0363-6119. PMID 27440717. 
  5. ↑ 5.0 5.1 5.2 "Regulation and physiological functions of phoenixin". Frontiers in Molecular Biosciences 9. 2022. doi:10.3389/fmolb.2022.956500. PMID 36090042. 
  6. ↑ 6.0 6.1 6.2 "A Novel CCK Receptor GPR173 Mediates Potentiation of GABAergic Inhibition". The Journal of Neuroscience 43 (13): 2305–2325. March 2023. doi:10.1523/JNEUROSCI.2035-22.2023. PMID 36813575. 
  7. ↑ 7.0 7.1 "Phoenixin: uncovering its receptor, signaling and functions" (in en). Acta Pharmacologica Sinica 39 (5): 774–778. May 2018. doi:10.1038/aps.2018.13. ISSN 1745-7254. PMID 29671415. 
  8. ↑ "Phoenixin Activates Immortalized GnRH and Kisspeptin Neurons Through the Novel Receptor GPR173". Molecular Endocrinology 30 (8): 872–888. 2016-08-01. doi:10.1210/me.2016-1039. ISSN 0888-8809. PMID 27268078. 
  9. ↑ McIlwraith, Emma K.; Loganathan, Neruja; Belsham, Denise D. (2019-04-05). "Regulation of Gpr173 expression, a putative phoenixin receptor, by saturated fatty acid palmitate and endocrine-disrupting chemical bisphenol A through a p38-mediated mechanism in immortalized hypothalamic neurons". Molecular and Cellular Endocrinology 485: 54–60. doi:10.1016/j.mce.2019.01.026. ISSN 0303-7207. https://www.sciencedirect.com/science/article/pii/S0303720719300383. 
  10. ↑ 10.0 10.1 10.2 Treen, Alice K.; Luo, Vicky; Belsham, Denise D. (August 2016). "Phoenixin Activates Immortalized GnRH and Kisspeptin Neurons Through the Novel Receptor GPR173". Molecular Endocrinology 30 (8): 872–888. doi:10.1210/me.2016-1039. ISSN 1944-9917. PMID 27268078. PMC 5414621. https://pmc.ncbi.nlm.nih.gov/articles/PMC5414621/. 
  11. ↑ 11.0 11.1 Nguyen, Xuan; Nakamura, Tomoko; Osuka, Satoko; Bayasula, Bayasula; Nakanishi, Natsuki; Kasahara, Yukiyo; Muraoka, Ayako; Hayashi, Shotaro et al. (July 2019). "Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis". Reproduction 158 (1): 25–34. https://rep.bioscientifica.com/view/journals/rep/158/1/REP-19-0025.xml. 
  12. ↑ 12.0 12.1 Yang, Yanwen; Lv, Yinglian; Liu, Junpeng; Zhang, Shuyun; Li, Yun; Shi, Yong (2020-04-01). "Phoenixin 20 promotes neuronal mitochondrial biogenesis via CREB–PGC-1α pathway" (in en). Journal of Molecular Histology 51 (2): 173–181. doi:10.1007/s10735-020-09867-8. ISSN 1567-2387. https://doi.org/10.1007/s10735-020-09867-8. 
  13. ↑ Billert, Maria; Wojciechowicz, Tatiana; Jasaszwili, Mariami; Szczepankiewicz, Dawid; Waśko, Jadwiga; Kaźmierczak, Sandra; Strowski, Mathias Z.; Nowak, Krzysztof W. et al. (2018-12-01). "Phoenixin-14 stimulates differentiation of 3T3-L1 preadipocytes via cAMP/Epac-dependent mechanism". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1863 (12): 1449–1457. doi:10.1016/j.bbalip.2018.09.006. ISSN 1388-1981. https://www.sciencedirect.com/science/article/pii/S1388198118302865. 
  14. ↑ Larco, Darwin; Cho-Clark, Madelaine; Mani, Shaila; Wu, T. John (1 February 2013). "The Metabolite GnRH-(1-5) Inhibits the Migration of Immortalized GnRH Neurons". Endocrinology 154 (2). doi:10.1210/en.2012-1746. PMID 23321696. https://academic.oup.com/endo/article/154/2/783/2423486. 
  15. ↑ 15.0 15.1 15.2 Larco, Darwin O.; Semsarzadeh, Nina N.; Cho-Clark, Madelaine; Mani, Shaila K.; Wu, T. John (2013-12-01). "β-Arrestin 2 Is a Mediator of GnRH-(1–5) Signaling in Immortalized GnRH Neurons" (in en). Endocrinology 154 (12): 4726–4736. doi:10.1210/en.2013-1286. ISSN 0013-7227. https://academic.oup.com/endo/article/154/12/4726/2433355. 



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