ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Peptide inhibitors disrupt the serotonin 5-HT2C receptor interaction with phosphatase and tensin homolog to allosterically modulate cellular signaling and behavior.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Allosteric Modulators of Serotonin Receptors: A Medicinal Chemistry Survey.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Heightened cocaine-seeking in male rats associates with a distinct transcriptomic profile in the medial prefrontal cortex.Frontiers in pharmacology · 2022Article
- Isolation housing elevates amphetamine seeking independent of nucleus accumbens glutamate receptor adaptations.The European journal of neuroscience · 2021Article
- Allosteric Modulator Leads Hiding in Plain Site: Developing Peptide and Peptidomimetics as GPCR Allosteric Modulators.Frontiers in chemistry · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- A Novel Synthetic Interfering Peptide Tat-3L4F Attenuates Olanzapine-Induced Weight Gain Through Disrupting Crosstalk Between Serotonin Receptor 2C and Protein Phosphatase and Tensin Homolog in Rats.The international journal of neuropsychopharmacology · 2020Article
- Serotonin 5-HTScientific reports · 2019Article
- Profile of cortical N-methyl-D-aspartate receptor subunit expression associates with inherent motor impulsivity in rats.Biochemical pharmacology · 2019Article
- Article
- Endogenous Serotonin 5-HTACS chemical neuroscience · 2019Article
- Conformational Dynamics and Allosteric Regulation Landscapes of Germline PTEN Mutations Associated with Autism Compared to Those Associated with Cancer.American journal of human genetics · 2019Article
- Design, Synthesis, and Characterization of 4-Undecylpiperidine-2-carboxamides as Positive Allosteric Modulators of the Serotonin (5-HT) 5-HTJournal of medicinal chemistry · 2019Article
- Allosteric Modulation of Class A GPCRs: Targets, Agents, and Emerging Concepts.Journal of medicinal chemistry · 2019Review
- The 5-HTThe Journal of pharmacology and experimental therapeutics · 2019Article
- Targeting the 5-HT2C Receptor in Biological Context and the Current State of 5-HT2C Receptor Ligand Development.Current topics in medicinal chemistry · 2019Review
- Article
- Novel Bivalent 5-HTACS chemical neuroscience · 2018Article
- Article
- Synthesis and Structure-Activity Relationships of Tool Compounds Based on WAY163909, a 5-HTACS chemical neuroscience · 2017Article
- Incubation of cocaine cue reactivity associates with neuroadaptations in the cortical serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system.Neuroscience · 2016Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 4 countries.
Funding
Abstract
Serotonin (5-hydroxytryptamine; 5-HT) signaling through the 5-HT(2C) receptor (5-HT(2C)R) is essential in normal physiology, whereas aberrant 5-HT(2C)R function is thought to contribute to the pathogenesis of multiple neural disorders. The 5-HT(2C)R interacts with specific protein partners, but the impact of such interactions on 5-HT(2C)R function is poorly understood. Here, we report convergent cellular and behavioral data that the interaction between the 5-HT(2C)R and protein phosphatase and tensin homolog (PTEN) serves as a regulatory mechanism to control 5-HT(2C)R-mediated biology but not that of the closely homologous 5-HT(2A)R. A peptide derived from the third intracellular loop of the human 5-HT(2C)R [3L4F (third loop, fourth fragment)] disrupted the association, allosterically augmented 5-HT(2C)R-mediated signaling in live cells, and acted as a positive allosteric modulator in rats in vivo. We identified the critical residues within an 8 aa fragment of the 3L4F peptide that maintained efficacy (within the picomolar range) in live cells similar to that of the 3L4F peptide. Last, molecular modeling identified key structural features and potential interaction sites of the active 3L4F peptides against PTEN. These compelling data demonstrate the specificity and importance of this protein assembly in cellular events and behaviors mediated by 5-HT(2C)R signaling and provide a chemical guidepost to the future development of drug-like peptide or small-molecule inhibitors as neuroprobes to study 5-HT(2C)R allostery and therapeutics for 5-HT(2C)R-mediated disorders.
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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.