8dpf Citations

Molecular insights into the regulation of constitutive activity by RNA editing of 5HT2C serotonin receptors.

OpenAccess logo Cell Rep 40 111211 (2022)
Related entries: 8dpg, 8dph, 8dpi

Cited: 24 times
EuropePMC logo PMID: 35977511

Abstract

RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These 5HT2C isoforms display differences in constitutive activity, agonist/inverse agonist potencies, and efficacies. To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state 5HT2C-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug lorcaserin (Belviq) and the classic psychedelic psilocin. We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 protein isoforms. Collectively, these findings reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities.

Reviews - 8dpf mentioned but not cited (2)

  1. A Novel "Activation Switch" Motif Common to All Aminergic Receptors. Lee KH, Manning JJ, Javitch J, Shi L. J Chem Inf Model 63 5001-5017 (2023)
  2. Structural studies of serotonin receptor family. Parajulee A, Kim K. BMB Rep 56 527-536 (2023)

Articles - 8dpf mentioned but not cited (5)



Reviews citing this publication (6)

  1. Psychedelics: preclinical insights provide directions for future research. Gumpper RH, Roth BL. Neuropsychopharmacology 49 119-127 (2024)
  2. The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology. Mastinu A, Anyanwu M, Carone M, Abate G, Bonini SA, Peron G, Tirelli E, Pucci M, Ribaudo G, Oselladore E, Premoli M, Gianoncelli A, Uberti DL, Memo M. Int J Mol Sci 24 1329 (2023)
  3. Molecular insights into GPCR mechanisms for drugs of abuse. Sanchez-Reyes OB, Zilberg G, McCorvy JD, Wacker D. J Biol Chem 299 105176 (2023)
  4. Exploring Novel Antidepressants Targeting G Protein-Coupled Receptors and Key Membrane Receptors Based on Molecular Structures. Yao H, Wang X, Chi J, Chen H, Liu Y, Yang J, Yu J, Ruan Y, Xiang X, Pi J, Xu JF. Molecules 29 964 (2024)
  5. G protein-coupled receptors as targets for transformative neuropsychiatric therapeutics. Schmitz GP, Roth BL. Am J Physiol Cell Physiol 325 C17-C28 (2023)
  6. The Effects of Psychedelics on Neuronal Physiology. Hatzipantelis CJ, Olson DE. Annu Rev Physiol 86 27-47 (2024)

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