ArticleJournal of cell science2005
Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane.
Article in Journal of cell science, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 164 citations in OpenAlex.
- The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling.Science signaling · 2025Article
- Identification of Potential Therapeutic Targets Against Anthrax-Toxin-Induced Liver and Heart Damage.Toxins · 2025Article
- Measuring Calcium-Sensing Receptor Agonist-Driven Insertional Signaling (ADIS) and Trafficking by TIRF Microscopy.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling.Chronic diseases and translational medicine · 2024Review
- Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.Pharmacological reviews · 2023Review
- Altered hair root gene expression profiles highlight calcium signaling and lipid metabolism pathways to be associated with curly hair initiation and maintenance in Mangalitza pigs.Frontiers in genetics · 2023Article
- GPCRs in Intracellular Compartments: New Targets for Drug Discovery.Biomolecules · 2022Review
- Glucagon receptor-mediated regulation of gluconeogenic gene transcription is endocytosis-dependent in primary hepatocytes.Molecular biology of the cell · 2022Article
- Functional Assessment of Calcium-Sensing Receptor Variants Confirms Familial Hypocalciuric Hypercalcemia.Journal of the Endocrine Society · 2022Article
- High Salt Upregulates CaThe Journal of pharmacology and experimental therapeutics · 2022Article
- Role of Satb1 and Satb2 Transcription Factors in the Glutamate Receptors Expression and CaInternational journal of molecular sciences · 2021Article
- Accelerated Development With Increased Bone Mass and Skeletal Response to Loading Suggest Receptor Activity Modifying Protein-3 as a Bone Anabolic Target.Frontiers in endocrinology · 2021Article
- The Calcium-Sensing Receptor Is Involved in Follicle-Stimulating Hormone-Induced Cumulus Expansion inFrontiers in cell and developmental biology · 2021Article
- Dawn of a New RAMPage.Trends in pharmacological sciences · 2020Review
- RAMPs as allosteric modulators of the calcitonin and calcitonin-like class B G protein-coupled receptors.Advances in pharmacology (San Diego, Calif.) · 2020Review
- Multiplexed analysis of the secretin-like GPCR-RAMP interactome.Science advances · 2019Article
- Mechanisms of the anterograde trafficking of GPCRs: Regulation of AT1R transport by interacting proteins and motifs.Traffic (Copenhagen, Denmark) · 2019Review
- hThe Journal of experimental medicine · 2018Article
- Interrelated role of Klotho and calcium-sensing receptor in parathyroid hormone synthesis and parathyroid hyperplasia.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate β-arrestin-biased signaling.Science signaling · 2018Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The calcium-sensing receptor (CaSR) is a class III G-protein-coupled receptor (GPCR) that responds to changes in extracellular calcium concentration and plays a crucial role in calcium homeostasis. The mechanisms controlling CaSR trafficking and surface expression are largely unknown. Using a CaSR tagged with the pH-sensitive GFP super-ecliptic pHluorin (SEP-CaSR), we show that delivery of the GPCR to the cell surface is dependent on receptor-activity-modifying proteins (RAMPs). We demonstrate that SEP-CaSRs are retained in the endoplasmic reticulum (ER) in COS7 cells that do not contain endogenous RAMPs whereas they are delivered to the plasma membrane in HEK 293 cells that do express RAMP1. Coexpression of RAMP1 or RAMP3, but not RAMP2, in COS7 cells was sufficient to target the CaSR to the cell surface. RAMP1 and RAMP3 colocalised and coimmunoprecipitated with the CaSR suggesting that these proteins associate within the cell. Our results indicate that RAMP expression promotes the forward trafficking of the GPCR from the ER to the Golgi apparatus and results in mature CaSR glycosylation, which is not observed in RAMP-deficient cells. Finally, silencing of RAMP1 in the endogenously expressing HEK293 cells using siRNA resulted in altered CaSR traffic. Taken together, our results show that the association with RAMPs is necessary and sufficient to transfer the immature CaSR retained in the ER towards the Golgi where it becomes fully glycosylated prior to delivery to the plasma membrane and demonstrate a role for RAMPs in the trafficking of a class III GPCR.
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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.