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Cited by 48RNA Research and SplicingIon channel regulation and functionNeuroscience and Neuropharmacology Research

The neuronal splicing factor Nova controls alternative splicing in N-type and P-type CaV2 calcium channels

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Allen, Summer E., Darnell, Robert B., Lipscombe, Diane·2010·Channels
DOI 10.4161/chan.4.6.12868PMC PMC3047467
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Abstract

Many cellular processes are involved in optimizing protein function for specific neuronal tasks; here we focus on alternative pre-mRNA splicing. Alternative pre-mRNA splicing gives cells the capacity to modify and selectively re-balance their existing pool of transcripts in a coordinated way across multiple mRNAs, thereby effecting relatively rapid and relatively stable changes in protein activity. Here we report on and discuss the coordinated regulation of two sites of alternative splicing, e24a and e31a, in P-type CaV2.1 and N-type CaV2.2 channels. These two exons encode 4 and 2 amino acids, respectively, in the extracellular linker regions between transmembrane spanning segments S3 and S4 in domains III and IV of each CaV2 subunit. Recent genome-wide screens of splicing factor-RNA binding events by Darnell and colleagues show that Nova-2 promotes inclusion of e24a in CaV2.2 mRNAs in brain. We review these studies and show that a homologous e24a is present in theCaV2 .1 gene, Cacna1a, and that it is expressed in different regions of the nervous system. Nova-2 enhances inclusion of e24a but represses e31a inclusion in CaV2.1 and CaV2.2 mRNAs in brain. It is likely that coordinated alternative pre-mRNA splicing across related CaV2 genes by common splicing factors, allows neurons to orchestrate changes in synaptic protein function while maintaining a balanced and functioning system.

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References 63 · Cited by 48

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Authors
Allen, S. E., Darnell, R. B., & Lipscombe, D.
Affiliations
  • Brown University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Lipscombe, Diane
ORCID
Venue
Channels
Publisher
Informa UK Limited
Published
2010-11-30
Volume
4
Issue
6
Pages
483-489
ISSN
  • 1933-6950 (ISSN-L)
  • 1933-6969
DOI
10.4161/chan.4.6.12868
PMC
PMC3047467
OpenAlex
W2021829595
Cited by
48
References
63
Citations by year
2025: 4 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 7 · 2012: 2
FWCI
0.42
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Channels (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Mental Health (R21MH087969)
  • National Institute of Neurological Disorders and Stroke (F31NS066691, R01 NS34389, R01NS029967, R01NS034389, R01NS29967, R01NS055251)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
alternative splicing, Cav2.1, CaV2.2, N-type calcium channels, P-type calcium channels, CACNA1A, neuronal calcium channels, brain
MeSH terms
Neuro-Oncological Ventral Antigen, Amino Acid Sequence, Animals, Antigens, Neoplasm, Binding Sites, Exons, Gene Expression Regulation, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, RNA Precursors, RNA, Messenger, RNA-Binding Proteins, Alternative Splicing, Calcium Channels, N-Type, Calcium Channels, P-Type, Calcium Channels, Q-Type, Mice

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