title: The G-protein coupled estrogen receptor, GPER: The inside and inside-out story.
abstract: GPER possesses structural and functional characteristics shared by members of the G-protein-coupled receptor (GPCR) superfamily, the largest class of plasma membrane receptors. This newly appreciated estrogen receptor is localized predominately within intracellular membranes in most, but not all, cell types and its surface expression is modulated by steroid hormones and during tissue injury. An intracellular staining pattern is not unique among GPCRs, which employ a diverse array of molecular mechanisms that restrict cell surface expression and effectively regulating receptor binding and activation. The finding that GPER displays an intracellular predisposition has created some confusion as the estrogen-inducible transcription factors, ERα and ERβ, also reside intracellularly, and has led to complex suggestions of receptor interaction. GPER undergoes constitutive retrograde trafficking from the plasma membrane to the endoplasmic reticulum and recent studies indicate its interaction with PDZ binding proteins that sort transmembrane receptors to synaptosomes and endosomes. Genetic targeting and selective ligand approaches as well as cell models that express GPER in the absence of ERs clearly supports GPER as a bonafide "stand alone" receptor. Here, the molecular details that regulate GPER action, its cell biological activities and its implicated roles in physiological and pathological processes are reviewed.
authors.affiliation: Wheaton College, Department of Chemistry, Norton, MA, 02766, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Gaudet
authors.affiliation: Women & Infants Hospital, Brown University, Providence, RI, 02903, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Cheng
authors.affiliation: Wheaton College, Department of Chemistry, Norton, MA, 02766, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Christensen
authors.affiliation: Rhode Island Hospital, Brown University, Providence, RI, 02903, USA. Electronic address: ejfilardo@gmail.com.
authors.forename: E J
authors.initials: EJ
authors.lastname: Filardo
mesh_terms: D000818:Animals; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D054731:PDZ Domains; D011485:Protein Binding; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C109584:GPER1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled
keywords: G protein-coupled receptor; GPER; Membrane estrogen receptor