ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Differential neuronal targeting of a new and two known calcium channel β4 subunit splice variants correlates with their regulation of gene expression.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- A biallelic mutation in CACNA2D2 associated with developmental and epileptic encephalopathy affects calcium channel-dependent as well as synaptic functions of αJournal of neurochemistry · 2025Article
- The membrane-associated β2e-subunit of voltage-gated calcium channels translocates to the nucleus and regulates gene expression.Frontiers in physiology · 2025Article
- Impacts of CACNB4 overexpression on dendritic spine density in both sexes and relevance to schizophrenia.Translational psychiatry · 2024Article
- Autism-Linked Mutations in αPharmaceuticals (Basel, Switzerland) · 2024Article
- Identification of Dp140 and α1-syntrophin as novel molecular interactors of the neuronal CaPflugers Archiv : European journal of physiology · 2023Article
- Article
- New Insights in CaVβ Subunits: Role in the Regulation of Gene Expression and Cellular Homeostasis.Frontiers in cell and developmental biology · 2022Review
- Whole-Exome Sequencing Identifies NovelFrontiers in pediatrics · 2022Article
- More than a pore: How voltage-gated calcium channels act on different levels of neuronal communication regulation.Channels (Austin, Tex.) · 2021Review
- Cav1.2 channelopathies causing autism: new hallmarks on Timothy syndrome.Pflugers Archiv : European journal of physiology · 2020Review
- Article
- Emerging roles for multifunctional ion channel auxiliary subunits in cancer.Cell calcium · 2019Review
- Presynaptic αThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- A Tripartite Interaction Among the Calcium Channel αFrontiers in cellular neuroscience · 2019Article
- Bicistronic CACNA1A Gene Expression in Neurons Derived from Spinocerebellar Ataxia Type 6 Patient-Induced Pluripotent Stem Cells.Stem cells and development · 2017Article
- Stapled Voltage-Gated Calcium Channel (CaACS chemical neuroscience · 2017Article
- Selective Loss of Smaller Spines in Schizophrenia.The American journal of psychiatry · 2017Article
- Trafficking of neuronal calcium channels.Neuronal signaling · 2017Review
- Loss of the calcium channel β4 subunit impairs parallel fibre volley and Purkinje cell firing in cerebellum of adult ataxic mice.The European journal of neuroscience · 2016Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The β subunits of voltage-gated calcium channels regulate surface expression and gating of CaV1 and CaV2 α1 subunits and thus contribute to neuronal excitability, neurotransmitter release, and calcium-induced gene regulation. In addition, certain β subunits are targeted into the nucleus, where they interact directly with the epigenetic machinery. Whereas their involvement in this multitude of functions is reflected by a great molecular heterogeneity of β isoforms derived from four genes and abundant alternative splicing, little is known about the roles of individual β variants in specific neuronal functions. In the present study, an alternatively spliced β4 subunit lacking the variable N terminus (β4e) is identified. It is highly expressed in mouse cerebellum and cultured cerebellar granule cells (CGCs) and modulates P/Q-type calcium currents in tsA201 cells and CaV2.1 surface expression in neurons. Compared with the other two known full-length β4 variants (β4a and β4b), β4e is most abundantly expressed in the distal axon, but lacks nuclear-targeting properties. To determine the importance of nuclear targeting of β4 subunits for transcriptional regulation, we performed whole-genome expression profiling of CGCs from lethargic (β4-null) mice individually reconstituted with β4a, β4b, and β4e. Notably, the number of genes regulated by each β4 splice variant correlated with the rank order of their nuclear-targeting properties (β4b > β4a > β4e). Together, these findings support isoform-specific functions of β4 splice variants in neurons, with β4b playing a dual role in channel modulation and gene regulation, whereas the newly detected β4e variant serves exclusively in calcium-channel-dependent functions.
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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.