GPR158 explained

Probable G-protein coupled receptor 158 (GPR158), also known as the metabotropic glycine receptor (mGlyR),^[1] is a protein that in humans is encoded by the GPR158 gene.^[2]

Function

This protein is an orphan class C GPCR. It is highly expressed in the brain, where it binds to RGS7, an inhibitor of G_i/o-coupled GPCR signaling, localizing it to the plasma membrane.^[3]

It is expressed at lower levels in other organs and shows an unusual subcellular localization pattern, being found at both the plasma membrane and in the nucleus.^[4]

Clinical significance

Role in mood regulation

GPR158 in the medial prefrontal cortex (mPFC) has been shown to regulate stress-induced depression in a mouse model of depression and has been found to be upregulated in post-mortem tissue samples from humans with major depressive disorder (MDD).^[5]

Role in prostate cancer

The GPR158 gene is an androgen-regulated gene that stimulates cell proliferation in prostate cancer cell lines, and it is linked to neuroendocrine differentiation.^[6]

Notes and References

1. Laboute T, Zucca S, Holcomb M, Patil DN, Garza C, Wheatley BA, Roy RN, Forli S, Martemyanov KA . Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR . Science . 379 . 6639 . 1352–1358 . March 2023 . 36996198 . 10.1126/science.add7150 . 10751545 . 2023Sci...379.1352L . 257836784 .
2. Web site: Entrez Gene: GPR158 G protein-coupled receptor 158.
3. Orlandi C, Posokhova E, Masuho I, Ray TA, Hasan N, Gregg RG, Martemyanov KA . GPR158/179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes . J. Cell Biol. . 197 . 6 . 711–9 . 2012 . 22689652 . 3373406 . 10.1083/jcb.201202123 .
4. Patel N, Itakura T, Gonzalez JM, Schwartz SG, Fini ME . GPR158, an orphan member of G protein-coupled receptor Family C: glucocorticoid-stimulated expression and novel nuclear role . PLOS ONE . 8 . 2 . e57843 . 2013 . 23451275 . 3581496 . 10.1371/journal.pone.0057843 . 2013PLoSO...857843P . free .
5. Sutton L, Orlandi C, Song C, Oh WC, Muntean BS, Xie K, Filippini A, Xie X, Satterfield R, Yaeger JD, Renner KJ, Young Jr SM, Xu B, Kwon H, Martemyanov KA . Orphan receptor GPR158 controls stress-induced depression . eLife . 2018 . 7 . 10.7554/eLife.33273.001 . 29419376 . 5823542 . free .
6. Patel N, Itakura T, Jeong S, Liao CP, Roy-Burman P, Zandi E, Groshen S, Pinski J, Coetzee GA, Gross ME, Fini ME . Expression and functional role of orphan receptor GPR158 in prostate cancer growth and progression . PLOS ONE . 10 . 2 . e0117758 . 2015 . 25693195 . 4333349 . 10.1371/journal.pone.0117758 . 2015PLoSO..1017758P . free .