ArticleScientific reports2018
Temporal reprogramming of calcium signalling via crosstalk of gonadotrophin receptors that associate as functionally asymmetric heteromers.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 67 citations in OpenAlex.
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- Single-molecule localization microscopy as a tool to quantify di/oligomerization of receptor tyrosine kinases and G protein-coupled receptors.Molecular pharmacology · 2025Review
- Mitochondrial Dynamics as Potential Modulators of Hormonal Therapy Effectiveness in Males.Biology · 2023Review
- Prostaglandin F2α requires activation of calcium-dependent signalling to trigger inflammation in human myometrium.Frontiers in endocrinology · 2023Article
- Allosteric modulation of gonadotropin receptors.Frontiers in endocrinology · 2023Review
- Functional rewiring of G protein-coupled receptor signaling in human labor.Cell reports · 2022Article
- Regulation of antral follicular growth by an interplay between gonadotropins and their receptors.Journal of assisted reproduction and genetics · 2022Review
- ERβ Regulation of Gonadotropin Responses during Folliculogenesis.International journal of molecular sciences · 2021Review
- Reduced FSH and LH action: implications for medically assisted reproduction.Human reproduction (Oxford, England) · 2021Review
- Cyclic AMP links luteinizing hormone signaling to dephosphorylation and inactivation of the NPR2 guanylyl cyclase in ovarian follicles†.Biology of reproduction · 2021Article
- The Luteinizing Hormone Receptor Knockout Mouse as a Tool to Probe the In Vivo Actions of Gonadotropic Hormones/Receptors in Females.Endocrinology · 2021Article
- Differential FSH Glycosylation Modulates FSHR Oligomerization and Subsequent cAMP Signaling.Frontiers in endocrinology · 2021Article
- Follicle-Stimulating Hormone Induces Lipid DropletsFrontiers in endocrinology · 2021Article
- Endocrine Disruption of the Follicle-Stimulating Hormone Receptor Signaling During the Human Antral Follicle Growth.Frontiers in endocrinology · 2021Review
- Recent advances in understanding gonadotropin signaling.Faculty reviews · 2021Review
- Article
- Human Recombinant FSH and Its Biosimilars: Clinical Efficacy, Safety, and Cost-Effectiveness in Controlled Ovarian Stimulation for In Vitro Fertilization.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Mechanistic insight into how gonadotropin hormone receptor complexes direct signaling†.Biology of reproduction · 2020Review
- FSH for the Treatment of Male Infertility.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Signal crosstalk between distinct G protein-coupled receptors (GPCRs) is one mechanism that underlies pleiotropic signalling. Such crosstalk is also pertinent for GPCRs activated by gonadotrophic hormones; follicle-stimulating hormone (FSH) and luteinising hormone (LH), with specific relevance to female reproduction. Here, we demonstrate that gonadotrophin receptor crosstalk alters LH-induced Gαq/11-calcium profiles. LH-induced calcium signals in both heterologous and primary human granulosa cells were prolonged by FSHR coexpression via influx of extracellular calcium in a receptor specific manner. LHR/FSHR crosstalk involves Gαq/11 activation as a Gαq/11 inhibitor abolished calcium responses. Interestingly, the enhanced LH-mediated calcium signalling induced by FSHR co-expression was dependent on intracellular calcium store release and involved Gβγ. Biophysical analysis of receptor and Gαq interactions indicated that ligand-dependent association between LHR and Gαq was rearranged in the presence of FSHR, enabling FSHR to closely associate with Gαq following LHR activation. This suggests that crosstalk may occur via close associations as heteromers. Super-resolution imaging revealed that LHR and FSHR formed constitutive heteromers at the plasma membrane. Intriguingly, the ratio of LHR:FSHR in heterotetramers was specifically altered following LH treatment. We propose that functionally significant FSHR/LHR crosstalk reprograms LH-mediated calcium signalling at the interface of receptor-G protein via formation of asymmetric complexes.
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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.