ArticleMolecular psychiatry2013
RNA splicing and editing modulation of 5-HT(2C) receptor function: relevance to anxiety and aggression in VGV mice.
Article in Molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 78 citations in OpenAlex.
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- Inhibitory effect of truncated isoforms on GPCR dimerization predicted by combinatorial computational strategy.Computational and structural biotechnology journal · 2024Article
- Connectivity and molecular profiles of Foxp2- and Dbx1-lineage neurons in the accessory olfactory bulb and medial amygdala.The Journal of comparative neurology · 2024Article
- Dynamic Dimerization of Chemokine Receptors and Potential Inhibitory Role of Their Truncated Isoforms Revealed through Combinatorial Prediction.International journal of molecular sciences · 2023Article
- Treadmill Exercise Improves Behavioral and Neurobiological Alterations in Restraint-Stressed Rats.Journal of molecular neuroscience : MN · 2023Article
- Molecular Docking and Dynamics Simulation Studies Predict Potential Anti-ADAR2 Inhibitors: Implications for the Treatment of Cancer, Neurological, Immunological and Infectious Diseases.International journal of molecular sciences · 2023Article
- RNA epitranscriptomics dysregulation: A major determinant for significantly increased risk of ASD pathogenesis.Frontiers in neuroscience · 2023Article
- Constitutive 5-HT2C receptor knock-out facilitates fear extinction through altered activity of a dorsal raphe-bed nucleus of the stria terminalis pathway.Translational psychiatry · 2022Article
- Adverse maternal environment affects hippocampal HTR2c variant expression and epigenetic characteristics in mouse offspring.Pediatric research · 2022Article
- Loss of CaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference.International journal of molecular sciences · 2022Review
- Serotonin 5-HTTranslational psychiatry · 2022Article
- Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants.Advances in neurobiology · 2021Article
- Conservation of A-to-I RNA editing in bowhead whale and pig.PloS one · 2021Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
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- Prader-Willi syndrome: reflections on seminal studies and future therapies.Open biology · 2020Review
- RNA Editing and Modifications in Mood Disorders.Genes · 2020Review
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Changes in serotonin(2C) receptor (5-HTR2c) editing, splicing and density were found in conditions such as depression and suicide, but mechanisms explaining the changes in 5-HTR2c function are unknown. Thus, mice expressing only the fully edited VGV isoform of 5-HTR2c, in which clinically relevant behavioral changes are associated with alterations in splicing and receptor density, were studied. VGV mice displayed enhanced anxiety-like behavior in response to a preferential 5-HTR2c agonist in the social interaction test. Nearly half of interactions between pairs of VGV congeners consisted of fighting behaviors, whereas no fighting occurred in wild-type (WT) mice. VGV mice also exhibited a striking increase in freezing behaviors in reaction to an innately aversive ultrasonic stimulus. This behavioral phenotype occurred in conjunction with decreased brain 5-HT turnover during stress. These functional data were put in relation with the 5-HTR2c mRNA splicing process generating a truncated protein (5-HTR2c-Tr) in addition to the full-length receptor (5-HTR2c-Fl). 5-HTR2c-Tr mRNA was less abundant in many brain regions of VGV mice, which concomitantly had more 5-HTR2c than WT mice. Fluorescence resonance energy transfer and bioluminescence resonance energy transfer studies in transfected living HEK293T cells showed that 5-HTR2c-Tr interacts with 5-HTR2c-Fl. The 5-HTR2c-Tr was localized in the endoplasmic reticulum where it retained 5-HTR2c-Fl, preventing the latter to reach the plasma membrane. Consequently, 5-HTR2c-Tr decreased (3)H-mesulergine binding to 5-HTR2c-Fl at the plasma membrane in a concentration-dependent manner and more strongly with edited 5-HTR2c-Fl. These results suggest that 5-HTR2c pre-mRNA editing and splicing are entwined processes determining increased 5-HTR2c levels in pathological conditions through a deficit in 5-HTR2c-Tr.
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