Transcription profiling of human HEK293 cells transfected with CavB4 or CavB4-R482X mutant cDNA
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ABSTRACT: Calcium channel B subunits (CavB) are mainly recognized for their contribution as regulatory subunits in modulating biophysical and trafficking channel properties. Here, we report for a novel function of the neuronal auxiliary CavB4 subunit in nuclear localization and transcriptional activity. In CA1 hippocampal neurons, nuclear translocation of CavB4 is differentiation-dependent. Similarly, in NG108-15 cell line, the nuclear localization of CavB4 is triggered by cAMP, a neuronal differentiating factor. The nuclear translocation of CavB4 requires an intact SH3 / GK interaction and is lost for a 38 amino acid C-terminal truncated form of the subunit implicated in human juvenile myoclonic epilepsy (CavB4-R482X mutant). The nuclear localization of CavB4 induces the regulation of numerous of genes which is not the case for the human mutation. These data indicate that gene regulation by a calcium channel subunit may contribute to the acquisition of a neuronal phenotype, a process that is disturbed if the nuclear localization is hampered by a mutation implicated in a severe neurological phenotype.
ORGANISM(S): Homo sapiens
SUBMITTER: Sylvain Baulande
PROVIDER: E-MEXP-1165 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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