ArticleMolecular endocrinology (Baltimore, Md.)2014
Dynamic kisspeptin receptor trafficking modulates kisspeptin-mediated calcium signaling.
Article in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
- Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders.The Journal of clinical investigation · 2020Trial
- A calcium-sensing receptor dileucine motif directs internalization to spatially distinct endosomal signaling pathways.iScience · 2025Article
- The Emerging Therapeutic Potential of Kisspeptin and Neurokinin B.Endocrine reviews · 2024Review
- Effect of CPP-related genes on GnRH secretion and Notch signaling pathway during puberty.Biomedical journal · 2023Review
- Heterozygous mutations in SOX2 may cause idiopathic hypogonadotropic hypogonadism via dominant-negative mechanisms.JCI insight · 2023Article
- Targeting hepatic kisspeptin receptor ameliorates nonalcoholic fatty liver disease in a mouse model.The Journal of clinical investigation · 2022Article
- Effects of kisspeptin incubation on the mature mouse testicular sperms quality: An experimental study.International journal of reproductive biomedicine · 2022Article
- Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer.Cell death & disease · 2020Article
- Pharmacological Programming of Endosomal Signaling Activated by Small Molecule Ligands of the Follicle Stimulating Hormone Receptor.Frontiers in pharmacology · 2020Article
- The matrix protein Fibulin-3 promotes KISS1R induced triple negative breast cancer cell invasion.Oncotarget · 2018Article
- Effect of Kisspeptin on the Developmental Competence and Early Transcript Expression in Porcine Oocytes Parthenogenetically Activated with Different Methods.BioMed research international · 2018Article
- G protein-coupled KISS1 receptor is overexpressed in triple negative breast cancer and promotes drug resistance.Scientific reports · 2017Article
- Dynamin Is Required for GnRH Signaling to L-Type Calcium Channels and Activation of ERK.Endocrinology · 2016Article
- Computational Analysis of Missense Variants of G Protein-Coupled Receptors Involved in the Neuroendocrine Regulation of Reproduction.Neuroendocrinology · 2016Article
- RF9 Acts as a KISS1R Agonist In Vivo and In Vitro.Endocrinology · 2015Article
- Minireview: Spatial Programming of G Protein-Coupled Receptor Activity: Decoding Signaling in Health and Disease.Molecular endocrinology (Baltimore, Md.) · 2015Review
- Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders.Endocrinology and metabolism (Seoul, Korea) · 2015Review
- Differential regulation of GnRH secretion in the preoptic area (POA) and the median eminence (ME) in male mice.Endocrinology · 2015Article
- KISS1R signals independently of Gαq/11 and triggers LH secretion via the β-arrestin pathway in the male mouse.Endocrinology · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Kisspeptin receptor (KISS1R) signaling plays a critical role in the regulation of reproduction. We investigated the role of kisspeptin-stimulated KISS1R internalization, recycling, and degradation in the modulation of KISS1R signaling. Kisspeptin stimulation of Chinese hamster ovary or GT1-7 cells expressing KISS1R resulted in a biphasic increase in intracellular Ca(2+) ([Ca(2+)]i), with a rapid acute increase followed by a more sustained second phase. In contrast, stimulation of the TRH receptor, another Gq/11-coupled receptor, resulted in a much smaller second-phase [Ca(2+)]i response. The KISS1R-mediated second-phase [Ca(2+)]i response was abolished by removal of kisspeptin from cell culture medium. Notably, the second-phase [Ca(2+)]i response was also inhibited by dynasore, brefeldin A, and phenylarsine oxide, which inhibit receptor internalization and recycling, suggesting that KISS1R trafficking contributes to the sustained [Ca(2+)]i response. We further demonstrated that KISS1R undergoes dynamic ligand-dependent and -independent recycling. We next investigated the fate of the internalized kisspeptin-KISS1R complex. Most internalized kisspeptin was released extracellularly in degraded form within 1 hour, suggesting rapid processing of the internalized kisspeptin-KISS1R complex. Using a biotinylation assay, we demonstrated that degradation of cell surface KISS1R was much slower than that of the internalized ligand, suggesting dissociated processing of the internalized kisspeptin-KISS1R complex. Taken together, our results suggest that the sustained calcium response to kisspeptin is dependent on the continued presence of extracellular ligand and is the result of dynamic KISS1R trafficking.
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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.