title: Activity and calcium regulate nuclear targeting of the calcium channel beta4b subunit in nerve and muscle cells.
abstract: Auxiliary beta subunits are critical determinants of membrane expression and gating properties of voltage-gated calcium channels. Mutations in the beta(4) subunit gene cause ataxia and epilepsy. However, the specific function of beta(4) in neurons and its causal relation to neurological diseases are unknown. Here we report the localization of the beta(4) subunit in the nuclei of cerebellar granule and Purkinje cells. beta(4b) was the only beta isoform showing nuclear targeting when expressed in neurons and skeletal myotubes. Its specific nuclear targeting property was mapped to an N-terminal double-arginine motif, which was necessary and sufficient for targeting beta subunits into the nucleus. Spontaneous electrical activity and calcium influx negatively regulated beta(4b) nuclear localization by a CRM-1-dependent nuclear export mechanism. The activity-dependent shuttling of beta(4b) into and out of the nucleus indicates a specific role of this beta subunit in neurons, in communicating the activity of calcium channels to the nucleus.
authors.affiliation: Department of Physiology and Medical Physics, Division of Physiology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Prakash
authors.initials: P
authors.lastname: Subramanyam
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Obermair
authors.forename: Sabine
authors.initials: S
authors.lastname: Baumgartner
authors.forename: Mathias
authors.initials: M
authors.lastname: Gebhart
authors.forename: Jörg
authors.initials: J
authors.lastname: Striessnig
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kaufmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Geley
authors.forename: Bernhard E
authors.initials: BE
authors.lastname: Flucher
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C491530:Cacnb4 protein, mouse; C491529:Cacnb4 protein, rat; D015220:Calcium Channels; D002118:Calcium