ArticleThe pharmacogenomics journal2007
PP2A-Bgamma subunit and KCNQ2 K+ channels in bipolar disorder.
Article in The pharmacogenomics journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Discovery of Novel Bicyclic Pyrazole Amides as Potent Neuronal KACS medicinal chemistry letters · 2026Article
- A distinct PP2A subunit regulates local protein phosphorylation at the axon initial segment.Nature communications · 2025Article
- Bipolar Disorder in a female with CDKL5 Deficiency Disorder: A Case Report.Research square · 2024Article
- GSK-3β Disrupts Neuronal Oscillatory Function to Inhibit Learning and Memory in Male Rats.Cellular and molecular neurobiology · 2022Article
- Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases.International journal of molecular sciences · 2022Review
- What is the Role of Lithium in Epilepsy?Current neuropharmacology · 2022Review
- Developmental Profile of Psychiatric Risk Associated With Voltage-Gated Cation Channel Activity.Biological psychiatry · 2021Article
- Protein phosphatase 2A - structure, function and role in neurodevelopmental disorders.Journal of cell science · 2021Review
- Neurological Disorders and Risk of Arrhythmia.International journal of molecular sciences · 2020Review
- Prefrontal inhibition of neuronal KBritish journal of pharmacology · 2020Article
- Article
- Differential Dorsolateral Prefrontal Cortex Proteomic Profiles of Suicide Victims with Mood Disorders.Genes · 2020Article
- Pharmacological Manipulation of KFrontiers in physiology · 2020Review
- Role of KCNQ potassium channels in stress-induced deficit of working memory.Neurobiology of stress · 2019Article
- Lithium improved behavioral and epileptic symptoms in an adolescent with ring chromosome 20 and bipolar disorder not otherwise specified.Clinical case reports · 2018Article
- A Schizophrenia-Related Deletion Leads to KCNQ2-Dependent Abnormal Dopaminergic Modulation of Prefrontal Cortical Interneuron Activity.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Protein Phosphatase 2A: a Double-Faced Phosphatase of Cellular System and Its Role in Neurodegenerative Disorders.Molecular neurobiology · 2018Review
- Modulation of Kv7 channels and excitability in the brain.Cellular and molecular life sciences : CMLS · 2017Review
- Autism spectrum disorder and epileptic encephalopathy: common causes, many questions.Journal of neurodevelopmental disorders · 2017Review
- AMIGO-Kv2.1 Potassium Channel Complex Is Associated With Schizophrenia-Related Phenotypes.Schizophrenia bulletin · 2016Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many bipolar affective disorder (BD) susceptibility loci have been identified but the molecular mechanisms responsible for the disease remain to be elucidated. In the locus 4p16, several candidate genes were identified but none of them was definitively shown to be associated with BD. In this region, the PPP2R2C gene encodes the Bgamma-regulatory subunit of the protein phosphatase 2A (PP2A-Bgamma). First, we identified, in two different populations, single nucleotide polymorphisms and risk haplotypes for this gene that are associated to BD. Then, we used the Bgamma subunit as bait to screen a human brain cDNA library with the yeast two-hybrid technique. This led us to two new splice variants of KCNQ2 channels and to the KCNQ2 channel itself. This unusual K+ channel has particularly interesting functional properties and belongs to a channel family that is already known to be implicated in several other monogenic diseases. In one of the BD populations, we also found a genetic association between the KCNQ2 gene and BD. We show that KCNQ2 splice variants differ from native channels by their shortened C-terminal sequences and are unique as they are active and exert a dominant-negative effect on KCNQ2 wild-type (wt) channel activity. We also show that the PP2A-Bgamma subunit significantly increases the current generated by KCNQ2wt, a channel normally inhibited by phosphorylation. The kinase glycogen synthase kinase 3 beta (GSK3beta) is considered as an interesting target of lithium, the classical drug used in BD. GSK3beta phosphorylates the KCNQ2 channel and this phosphorylation is decreased by Li+.
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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.