ArticleThe Journal of biological chemistry2011
Down-modulation of the G-protein-coupled estrogen receptor, GPER, from the cell surface occurs via a trans-Golgi-proteasome pathway.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Cytoplasmic G Protein-Coupled Estrogen Receptor 1 as a Prognostic Indicator of Breast Cancer: A Meta-Analysis.Technology in cancer research & treatmentPooled it
- More than alternative estrogen receptors: the emerging role of GPER-1 and ERα36 in breast cancer.Exploration of targeted anti-tumor therapy · 2026Review
- The beta1-adrenergic receptor in the heart.Cell death discovery · 2025Review
- Mechanisms of bisphenol A and its analogs as endocrine disruptors via nuclear receptors and related signaling pathways.Archives of toxicology · 2025Review
- Decoding estrogen receptor and GPER biology: structural insights and therapeutic advances in ERα-positive breast cancer.Frontiers in oncology · 2025Review
- Review
- Current progress and prospects for G protein-coupled estrogen receptor in triple-negative breast cancer.Frontiers in cell and developmental biology · 2024Review
- Tamoxifen Activates Transcription Factor EB and Triggers Protective Autophagy in Breast Cancer Cells by Inducing Lysosomal Calcium Release: A Gateway to the Onset of Endocrine Resistance.International journal of molecular sciences · 2023Article
- Identification of novel pathogenic roles of BLZF1/ATF6 in tumorigenesis of gastrointestinal stromal tumor showing Golgi-localized mutant KIT.Cell death and differentiation · 2023Article
- The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology.Biomolecules · 2023Review
- Connecting G protein-coupled estrogen receptor biomolecular mechanisms with the pathophysiology of preeclampsia: a review.Reproductive biology and endocrinology : RB&E · 2023Review
- The effects of GPER on age-associated memory impairment induced by decreased estrogen levels.Frontiers in molecular biosciences · 2023Review
- The emerging role of estrogen's non-nuclear signaling in the cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- Expression and estrogen regulation of G protein-coupled estrogen receptor in human glioblastoma cells.Oncology letters · 2022Article
- Proliferation and apoptosis regulation by G protein-coupled estrogen receptor in glioblastoma C6 cells.Oncology letters · 2022Article
- Estrogen alleviates hepatocyte necroptosis depending on GPER in hepatic ischemia reperfusion injury.Journal of physiology and biochemistry · 2022Article
- Berberine Inhibits MDA-MB-231 Cells as an Agonist of G Protein-Coupled Estrogen Receptor 1.International journal of molecular sciences · 2021Article
- Ligand-Independent G Protein-Coupled Estrogen Receptor/G Protein-Coupled Receptor 30 Activity: Lack of Receptor-Dependent Effects of G-1 and 17Molecular pharmacology · 2021Article
- The Sex-Related Interplay between TME and Cancer: On the Critical Role of Estrogen, MicroRNAs and Autophagy.Cancers · 2021Review
- Proteolytic Targeting Chimeras with Specificity for Plasma Membrane and Intracellular Estrogen Receptors.Molecular pharmaceutics · 2021Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
GPER is a G(s)-coupled seven-transmembrane receptor that has been linked to specific estrogen binding and signaling activities that are manifested by plasma membrane-associated enzymes. However, in many cell types, GPER is predominately localized to the endoplasmic reticulum (ER), and only minor amounts of receptor are detectable at the cell surface, an observation that has caused controversy regarding its role as a plasma membrane estrogen receptor. Here, we show that GPER constitutively buds intracellularly into EEA-1+ endosomes from clathrin-coated pits. Nonvisual arrestins-2/-3 do not co-localize with GPER, and expression of arrestin-2 dominant-negative mutants lacking clathrin- or β-adaptin interaction sites fails to block GPER internalization suggesting that arrestins are not involved in GPER endocytosis. Like β1AR, which recycles to the plasma membrane, GPER co-traffics with transferrin+, Rab11+ recycling endosomes. However, endocytosed GPER does not recycle to the cell surface, but instead returns to the trans-Golgi network (TGN) and does not re-enter the ER. GPER is ubiquitinated at the cell surface, exhibits a short half-life (t½;) <1 h), and is protected from degradation by the proteasome inhibitor, MG132. Disruption of the TGN by brefeldin A induces the accumulation of endocytosed GPER in Rab11+ perinuclear endosomes and prevents GPER degradation. Our results provide an explanation as to why GPER is not readily detected on the cell surface in some cell types and further suggest that TGN serves as the checkpoint for degradation of endocytosed GPER.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.