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Nuclear life of the voltage-gated Cacnb4 subunit and its role in gene transcription regulation
- Source :
- Channels (Austin), Channels (Austin), 2013, 7 (2), pp.119-25. ⟨10.4161/chan.23895⟩
- Publication Year :
- 2013
- Publisher :
- Informa UK Limited, 2013.
-
Abstract
- International audience; The pore-forming subunit of voltage-gated calcium channels is associated to auxiliary subunits among which the cytoplasmic β subunit. The different isoforms of this subunit control both the plasma membrane targeting and the biophysical properties of the channel moiety. In a recent study, we demonstrated that the Cacnb4 (β 4) isoform is at the center of a new signaling pathway that connects neuronal excitability and gene transcription. This mechanism relies on nuclear targeting of β 4 triggered by neuronal electrical stimulation. This re-localization of β 4 is promoted by its interaction with Ppp2r5d a regulatory subunit of PP2A in complex with PP2A itself. The formation, as well as the nuclear translocation, of the β 4/ Ppp2r5d/ PP2A complex is totally impaired by the premature R482X stops mutation of β 4 that has been previously associated with juvenile epilepsy. Taking as a case study the tyrosine hydroxylase gene that is strongly upregulated in brain of lethargic mice, deficient for β 4 expression, we deciphered the molecular steps presiding to this signaling pathway. Here we show that expression of wild-type β 4 in HEK293 cells results in the regulation of several genes, while expression of the mutated β 4 (β 1-481) produces a different set of gene regulation. Several genes regulated by β 4 in HEK293 cells were also regulated upon neuronal differentiation of NG108-15 cells that induces nuclear translocation of β 4 suggesting a link between β 4 nuclear targeting and gene regulation.
- Subjects :
- Voltage-gated calcium channel
HP1γ
Gene isoform
Transcription, Genetic
Tyrosine 3-Monooxygenase
Neurogenesis
Protein subunit
Active Transport, Cell Nucleus
Biophysics
CACNB4
Biochemistry
Mice
tyrosine hydroxylase
medicine
Animals
Humans
phosphatase 2A
Gene Regulatory Networks
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Protein Phosphatase 2
Cell Nucleus
Neurons
Regulation of gene expression
biology
HEK 293 cells
Protein phosphatase 2
gene transcription regulation
Molecular biology
Article Addendum
Protein Subunits
Cell nucleus
HEK293 Cells
medicine.anatomical_structure
Gene Expression Regulation
β4 subunit
Mutation
biology.protein
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Calcium Channels
Signal transduction
Signal Transduction
thyroid receptor alpha
Subjects
Details
- ISSN :
- 19336969 and 19336950
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Channels
- Accession number :
- edsair.doi.dedup.....39fda210a8267f40788db8502d5fe440