ArticlePloS one2010
The human gonadotropin releasing hormone type I receptor is a functional intracellular GPCR expressed on the nuclear membrane.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
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- Mast cell corticotropin-releasing factor subtype 2 suppresses mast cell degranulation and limits the severity of anaphylaxis and stress-induced intestinal permeability.The Journal of allergy and clinical immunology · 2019Article
- GnRH-A Key Regulator of FSH.Endocrinology · 2019Review
- GPCR signalling from within the cell.British journal of pharmacology · 2018Review
- Intracellular GPCRs Play Key Roles in Synaptic Plasticity.ACS chemical neuroscience · 2018Review
- Gonadotropin regulation by pulsatile GnRH: Signaling and gene expression.Molecular and cellular endocrinology · 2018Review
- Article
- Association of miR-938G>A Polymorphisms with Primary Ovarian Insufficiency (POI)-Related Gene Expression.International journal of molecular sciences · 2017Article
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- Molecular determinants of the human α2C-adrenergic receptor temperature-sensitive intracellular traffic.Molecular pharmacology · 2015Article
- Targeting G protein coupled receptor-related pathways as emerging molecular therapies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2015Review
- Androgen receptor and chemokine receptors 4 and 7 form a signaling axis to regulate CXCL12-dependent cellular motility.BMC cancer · 2015Article
- Nuclear compartmentalization of α1-adrenergic receptor signaling in adult cardiac myocytes.Journal of cardiovascular pharmacology · 2015Review
- Osteoblast regulation via ligand-activated nuclear trafficking of the oxytocin receptor.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- KISS1R signals independently of Gαq/11 and triggers LH secretion via the β-arrestin pathway in the male mouse.Endocrinology · 2014Article
- Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance.Pharmacological reviews · 2014Review
- Article
- G protein-coupled receptor signalling in the cardiac nuclear membrane: evidence and possible roles in physiological and pathophysiological function.The Journal of physiology · 2012Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
The mammalian type I gonadotropin releasing hormone receptor (GnRH-R) is a structurally unique G protein-coupled receptor (GPCR) that lacks cytoplasmic tail sequences and displays inefficient plasma membrane expression (PME). Compared to its murine counterparts, the primate type I receptor is inefficiently folded and retained in the endoplasmic reticulum (ER) leading to a further reduction in PME. The decrease in PME and concomitant increase in intracellular localization of the mammalian GnRH-RI led us to characterize the spatial distribution of the human and mouse GnRH receptors in two human cell lines, HEK 293 and HTR-8/SVneo. In both human cell lines we found the receptors were expressed in the cytoplasm and were associated with the ER and nuclear membrane. A molecular analysis of the receptor protein sequence led us to identify a putative monopartite nuclear localization sequence (NLS) in the first intracellular loop of GnRH-RI. Surprisingly, however, neither the deletion of the NLS nor the addition of the Xenopus GnRH-R cytoplasmic tail sequences to the human receptor altered its spatial distribution. Finally, we demonstrate that GnRH treatment of nuclei isolated from HEK 293 cells expressing exogenous GnRH-RI triggers a significant increase in the acetylation and phosphorylation of histone H3, thereby revealing that the nuclear-localized receptor is functional. Based on our findings, we conclude that the mammalian GnRH-RI is an intracellular GPCR that is expressed on the nuclear membrane. This major and novel discovery causes us to reassess the signaling potential of this physiologically and clinically important receptor.
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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.