ArticleThe Journal of biological chemistry2012
ARF6 activated by the LHCG receptor through the cytohesin family of guanine nucleotide exchange factors mediates the receptor internalization and signaling.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- LHCGR phamacodynamic effects during follicular maturation.Frontiers in endocrinology · 2026Review
- Luteinizing Hormone Receptor Mutation (LHRInterdisciplinary sciences, computational life sciences · 2024Article
- Article
- Molecular Analysis of SARS-CoV-2 Spike Protein-Induced Endothelial Cell Permeability and vWF Secretion.International journal of molecular sciences · 2023Article
- Targeting of the Interleukin-13 Receptor (IL-13R)α2 Expressing Prostate Cancer by a Novel Hybrid Lytic Peptide.Biomolecules · 2023Article
- Does coupling to ADP ribosylation factor 6 explain differences between muscarinic and other receptors in interaction with β-adrenoceptor-mediated smooth muscle relaxation?Naunyn-Schmiedeberg's archives of pharmacology · 2022Review
- Recent advances in understanding gonadotropin signaling.Faculty reviews · 2021Review
- Pan-Cancer Analysis of NOS3 Identifies Its Expression and Clinical Relevance in Gastric Cancer.Frontiers in oncology · 2021Article
- Mechanistic insight into how gonadotropin hormone receptor complexes direct signaling†.Biology of reproduction · 2020Review
- CLIC4/Arf6 Pathway.Circulation research · 2019Article
- The small GTPase ARF6 regulates protein trafficking to control cellular function during development and in disease.Small GTPases · 2019Article
- Article
- Ultrastructural Localization of Endogenous Exchange Factor for ARF6 in Adrenocortical Cells In Situ of Mice.Acta histochemica et cytochemica · 2016Article
- D-Aspartic acid stimulates steroidogenesis through the delay of LH receptor internalization in a mammalian Leydig cell line.Journal of endocrinological investigation · 2016Article
- RLIP76 regulates Arf6-dependent cell spreading and migration by linking ARNO with activated R-Ras at recycling endosomes.Biochemical and biophysical research communications · 2015Article
- Structure-activity relationship studies of QS11, a small molecule Wnt synergistic agonist.Bioorganic & medicinal chemistry letters · 2015Article
- Activation of the Small G Protein Arf6 by Dynamin2 through Guanine Nucleotide Exchange Factors in Endocytosis.Scientific reports · 2015Article
- Regulators and Effectors of Arf GTPases in Neutrophils.Journal of immunology research · 2015Review
- The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell surface expression.Scientific reports · 2014Article
- Exchange factor EFA6R requires C-terminal targeting to the plasma membrane to promote cytoskeletal rearrangement through the activation of ADP-ribosylation factor 6 (ARF6).The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The luteinizing hormone chorionic gonadotropin receptor (LHCGR) is a G(s)-coupled GPCR that is essential for the maturation and function of the ovary and testis. LHCGR is internalized following its activation, which regulates the biological responsiveness of the receptor. Previous studies indicated that ADP-ribosylation factor (ARF)6 and its GTP-exchange factor (GEF) cytohesin 2 regulate LHCGR internalization in follicular membranes. However, the mechanisms by which ARF6 and cytohesin 2 regulate LHCGR internalization remain incompletely understood. Here we investigated the role of the ARF6 signaling pathway in the internalization of heterologously expressed human LHCGR (HLHCGR) in intact cells using a combination of pharmacological inhibitors, siRNA and the expression of mutant proteins. We found that human CG (HCG)-induced HLHCGR internalization, cAMP accumulation and ARF6 activation were inhibited by Gallein (βγ inhibitor), Wortmannin (PI 3-kinase inhibitor), SecinH3 (cytohesin ARF GEF inhibitor), QS11 (an ARF GAP inhibitor), an ARF6 inhibitory peptide and ARF6 siRNA. However, Dynasore (dynamin inhibitor), the dominant negative mutants of NM23-H1 (dynamin activator) and clathrin, and PBP10 (PtdIns 4,5-P2-binding peptide) inhibited agonist-induced HLHCGR and cAMP accumulation but not ARF6 activation. These results indicate that heterotrimeric G-protein, phosphatidylinositol (PI) 3-kinase (PI3K), cytohesin ARF GEF and ARF GAP function upstream of ARF6 whereas dynamin and clathrin act downstream of ARF6 in the regulation of HCG-induced HLHCGR internalization and signaling. In conclusion, we have identified the components and molecular details of the ARF6 signaling pathway required for agonist-induced HLHCGR internalization.
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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.