ArticleNature chemical biology2014
Cdk5 induces constitutive activation of 5-HT6 receptors to promote neurite growth.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 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
59 citing papers in PubMed, 115 citations in OpenAlex.
- Dually Acting Ligands Targeting Serotonin Receptors: Implications in CNS Disorders.Journal of medicinal chemistry · 2026Review
- Serotonin Modulation of Dorsoventral Hippocampus in Physiology and Schizophrenia.International journal of molecular sciences · 2025Review
- Novel 5-HTScientific reports · 2025Article
- The Primary Cilia are Associated with the Axon Initial Segment in Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Long-Chain Cyclic Arylguanidines as Multifunctional Serotonin Receptor Ligands with Antiproliferative Activity.ACS omega · 2025Article
- Low-Basicity 5-HTInternational journal of molecular sciences · 2024Article
- Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges.Communications biology · 2024Article
- Structural determinants for activation of the Tau kinase CDK5 by the serotonin receptor 5-HT7R.Cell communication and signaling : CCS · 2024Article
- Superiority of the Triple-Acting 5-HTJournal of medicinal chemistry · 2023Article
- Diabetic Neuropathic Pain and Serotonin: What Is New in the Last 15 Years?Biomedicines · 2023Review
- Structural insights into constitutive activity of 5-HTProceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Constitutive Activity of Spinal 5-HTBiomolecules · 2023Article
- Impact of 5-HTCells · 2023Review
- Impact of the Substitution Pattern at the Basic Center and Geometry of the Amine Fragment on 5-HTMolecules (Basel, Switzerland) · 2023Article
- Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model.Frontiers in neuroscience · 2023Article
- 1-(Arylsulfonyl-isoindol-2-yl)piperazines as 5-HTBiomolecules · 2022Article
- A transgenic zebrafish forOpen biology · 2022Article
- Three decades of Cdk5.Journal of biomedical science · 2021Review
- Structure-Based Design and Optimization of FPPQ, a Dual-Acting 5-HTJournal of medicinal chemistry · 2021Article
- 5-HT Receptors and the Development of New Antidepressants.International journal of molecular sciences · 2021Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serotonin6 receptor (5-HT6R) is a promising target for treating cognitive deficits of schizophrenia often linked to alterations of neuronal development. This receptor controls neurodevelopmental processes, but the signaling mechanisms involved remain poorly understood. Using a proteomic strategy, we show that 5-HT6Rs constitutively interact with cyclin-dependent kinase 5 (Cdk5). Expression of 5-HT6Rs in NG108-15 cells induced neurite growth and expression of voltage-gated Ca(2+) channels, two hallmarks of neuronal differentiation. 5-HT6R-elicited neurite growth was agonist independent and prevented by the 5-HT6R antagonist SB258585, which behaved as an inverse agonist. Moreover, it required receptor phosphorylation at Ser350 by Cdk5 and Cdc42 activity. Supporting a role of native 5-HT6Rs in neuronal differentiation, neurite growth of primary neurons was reduced by SB258585, by silencing 5-HT6R expression or by mutating Ser350 into alanine. These results reveal a functional interplay between Cdk5 and a G protein-coupled receptor to control neuronal differentiation.
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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.