ArticleThe EMBO journal2012
Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy.
Article in The EMBO journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- N-Type Ca Channel in Epileptic Syndromes and Epilepsy: A Systematic Review of Its Genetic Variants.International journal of molecular sciences · 2023Pooled it
- The Cavβ4 subunit of Cav1.2 channels antagonizes isoproterenol-induced hypertrophy in rat cardiac muscle cells by down-regulating miR-183-5p.Physiological reports · 2026Article
- Extracellular vesicles derived from engineered BMSCs improve damaged cartilage in mice with osteoarthritis by delivering PBX1.Stem cell research & therapy · 2026Article
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- CACNB4 attenuates cardiac dysfunction by regulating calcium and ATP levels via interaction with RyR2.European journal of medical research · 2025Article
- KChIP3 fosters neuroinflammation and synaptic dysfunction in the 5XFAD mouse model of Alzheimer's disease.Journal of neuroinflammation · 2025Article
- Pathogenic de novo variants in PPP2R5C cause a neurodevelopmental disorder within the Houge-Janssens syndrome spectrum.American journal of human genetics · 2025Article
- The membrane-associated β2e-subunit of voltage-gated calcium channels translocates to the nucleus and regulates gene expression.Frontiers in physiology · 2025Article
- Thyroid Hormone Upregulates Cav1.2 Channels in Cardiac Cells via the Downregulation of the Channels' β4 Subunit.International journal of molecular sciences · 2024Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- Calcium Channels in Retinal Function and Disease.Annual review of vision science · 2022Review
- New Insights in CaVβ Subunits: Role in the Regulation of Gene Expression and Cellular Homeostasis.Frontiers in cell and developmental biology · 2022Review
- More than a pore: How voltage-gated calcium channels act on different levels of neuronal communication regulation.Channels (Austin, Tex.) · 2021Review
- Proteomic and Transcriptomic Analyses Reveal Pathological Changes in the Entorhinal Cortex Region that Correlate Well with Dysregulation of Ion Transport in Patients with Alzheimer's Disease.Molecular neurobiology · 2021Article
- Nanoenviroments of the β-Subunit of L-Type Voltage-Gated Calcium Channels in Adult Cardiomyocytes.Frontiers in cell and developmental biology · 2021Article
- Cav1.2 channelopathies causing autism: new hallmarks on Timothy syndrome.Pflugers Archiv : European journal of physiology · 2020Review
- Article
- PPP2R5D-Related Intellectual Disability and Neurodevelopmental Delay: A Review of the Current Understanding of the Genetics and Biochemical Basis of the Disorder.International journal of molecular sciences · 2020Review
- Emerging roles for multifunctional ion channel auxiliary subunits in cancer.Cell calcium · 2019Review
- Expanding the Spectrum of BAF-Related Disorders: De Novo Variants in SMARCC2 Cause a Syndrome with Intellectual Disability and Developmental Delay.American journal of human genetics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcium current through voltage-gated calcium channels (VGCC) controls gene expression. Here, we describe a novel signalling pathway in which the VGCC Cacnb4 subunit directly couples neuronal excitability to transcription. Electrical activity induces Cacnb4 association to Ppp2r5d, a regulatory subunit of PP2A phosphatase, followed by (i) nuclear translocation of Cacnb4/Ppp2r5d/PP2A, (ii) association with the tyrosine hydroxylase (TH) gene promoter through the nuclear transcription factor thyroid hormone receptor alpha (TRα), and (iii) histone binding through association of Cacnb4 with HP1γ concomitantly with Ser(10) histone H3 dephosphorylation by PP2A. This signalling cascade leads to TH gene repression by Cacnb4 and is controlled by the state of interaction between the SH3 and guanylate kinase (GK) modules of Cacnb4. The human R482X CACNB4 mutation, responsible for a form of juvenile myoclonic epilepsy, prevents association with Ppp2r5 and nuclear targeting of the complex by altering Cacnb4 conformation. These findings demonstrate that an intact VGCC subunit acts as a repressor recruiting platform to control neuronal gene expression.
Indexed as
Identifiers
What OpenQuestion holds
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.