Membrane estrogen receptor

Membrane estrogen receptors (mERs) are a group of receptors which bind estrogen.[1][2] Unlike nuclear estrogen receptors, which mediate their effects via slower genomic mechanisms, mERs are cell surface receptors that rapidly alter cell signaling via modulation of intracellular signaling cascades.[3][4]

Nuclear estrogen receptors such as ERα and ERβ become mERs through palmitoylation, a post-translational modification that enhances ER association with caveolin-1 to enable trafficking of ERs to the membrane or membrane caveolae.[5][6] Other putative mERs include GPER (GPR30), GPRC6A, ER-X, ERx and Gq-mER.[3][7][8][9]

membrane ER localization by caveolins following palmitoylation.
ERα/ERβ becoming mERs through trafficking to the membrane by caveolins, following palmitoylation.
  1. ^ Soltysik K, Czekaj P (April 2013). "Membrane estrogen receptors - is it an alternative way of estrogen action?". Journal of Physiology and Pharmacology. 64 (2): 129–142. PMID 23756388.
  2. ^ Micevych PE, Kelly MJ (2012). "Membrane estrogen receptor regulation of hypothalamic function". Neuroendocrinology. 96 (2): 103–110. doi:10.1159/000338400. PMC 3496782. PMID 22538318.
  3. ^ a b Micevych PE, Mermelstein PG (August 2008). "Membrane estrogen receptors acting through metabotropic glutamate receptors: an emerging mechanism of estrogen action in brain". Molecular Neurobiology. 38 (1): 66–77. doi:10.1007/s12035-008-8034-z. PMC 2663000. PMID 18670908.
  4. ^ Razandi M, Pedram A, Greene GL, Levin ER (February 1999). "Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERalpha and ERbeta expressed in Chinese hamster ovary cells". Molecular Endocrinology. 13 (2): 307–319. doi:10.1210/mend.13.2.0239. PMID 9973260.
  5. ^ Razandi M, Alton G, Pedram A, Ghonshani S, Webb P, Levin ER (March 2003). "Identification of a structural determinant necessary for the localization and function of estrogen receptor alpha at the plasma membrane". Molecular and Cellular Biology. 23 (5): 1633–1646. doi:10.1128/MCB.23.5.1633-1646.2003. PMC 151696. PMID 12588983.
  6. ^ Levin ER (December 2009). "Plasma membrane estrogen receptors". Trends in Endocrinology and Metabolism. 20 (10): 477–482. doi:10.1016/j.tem.2009.06.009. PMC 3589572. PMID 19783454.
  7. ^ Micevych PE, Kelly MJ (2012). "Membrane estrogen receptor regulation of hypothalamic function". Neuroendocrinology. 96 (2): 103–110. doi:10.1159/000338400. PMC 3496782. PMID 22538318.
  8. ^ Pi M, Parrill AL, Quarles LD (December 2010). "GPRC6A mediates the non-genomic effects of steroids". The Journal of Biological Chemistry. 285 (51): 39953–39964. doi:10.1074/jbc.M110.158063. PMC 3000977. PMID 20947496.
  9. ^ Arnal JF, Lenfant F, Metivier R, Flouriot G, Henrion D, Adlanmerini M, et al. (July 2017). "Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications". Physiological Reviews. 97 (3): 1045–1087. doi:10.1152/physrev.00024.2016. PMID 28539435. S2CID 42396301.