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J Neurosci
2006 Mar 08;2610:2635-44. doi: 10.1523/JNEUROSCI.0067-06.2006.
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Alternative splicing of the voltage-gated Ca2+ channel beta4 subunit creates a uniquely folded N-terminal protein binding domain with cell-specific expression in the cerebellar cortex.
Vendel AC
,
Terry MD
,
Striegel AR
,
Iverson NM
,
Leuranguer V
,
Rithner CD
,
Lyons BA
,
Pickard GE
,
Tobet SA
,
Horne WA
.
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Ca2+ channel beta subunits regulate cell-surface expression and gating of voltage-dependent Ca2+ channel alpha1 subunits. Based on primary sequence comparisons, beta subunits are predicted to be modular structures composed of five domains (A-E) that are related to the large family of membrane-associated guanylate kinase proteins. The crystal structure of the beta subunit core B-D domains has been reported recently; however, little is known about the structures of the A and E domains. The N-terminal A domain differs among the four subtypes of Ca2+ channel beta subunits (beta1-beta4) primarily as the result of two duplications of an ancestral gene containing multiple alternatively spliced exons. At least nine A domain sequences can be generated by alternative splicing. In this report, we focus on one A domain sequence, the highly conserved beta4a A domain. We solved its three-dimensional structure and show that it is expressed in punctate structures throughout the molecular layer of the cerebellar cortex. We also demonstrate that it does not participate directly in Cav2.1 Ca2+ channel gating but serves as a binding site in protein-protein interactions with synaptotagmin I and the LC2 domain of microtubule-associated protein 1A. With respect to beta4 subunits, the interactions are specific for the beta4a splice variant, because they do not occur with the beta4b A domain. These results have strong bearing on our current understanding of the structure of alternatively spliced Ca2+ channel beta subunits and the cell-specific roles they play in the CNS.
Bell,
Cell-specific alternative splicing increases calcium channel current density in the pain pathway.
2004, Pubmed
Bell,
Cell-specific alternative splicing increases calcium channel current density in the pain pathway.
2004,
Pubmed
Bourinet,
Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.
1999,
Pubmed
,
Xenbase
Brünger,
Crystallography & NMR system: A new software suite for macromolecular structure determination.
1998,
Pubmed
Cantí,
Evidence for two concentration-dependent processes for beta-subunit effects on alpha1B calcium channels.
2001,
Pubmed
,
Xenbase
Chaudhuri,
Alternative splicing as a molecular switch for Ca2+/calmodulin-dependent facilitation of P/Q-type Ca2+ channels.
2004,
Pubmed
Chen,
Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels.
2004,
Pubmed
Cohen,
The C2A domain of synaptotagmin alters the kinetics of voltage-gated Ca2+ channels Ca(v)1.2 (Lc-type) and Ca(v)2.3 (R-type).
2003,
Pubmed
,
Xenbase
Delaglio,
NMRPipe: a multidimensional spectral processing system based on UNIX pipes.
1995,
Pubmed
Foell,
Molecular heterogeneity of calcium channel beta-subunits in canine and human heart: evidence for differential subcellular localization.
2004,
Pubmed
Hanlon,
Modelling of a voltage-dependent Ca2+ channel beta subunit as a basis for understanding its functional properties.
1999,
Pubmed
Helton,
Alternative splicing of the beta 4 subunit has alpha1 subunit subtype-specific effects on Ca2+ channel gating.
2002,
Pubmed
,
Xenbase
Helton,
Alternative splicing of a beta4 subunit proline-rich motif regulates voltage-dependent gating and toxin block of Cav2.1 Ca2+ channels.
2002,
Pubmed
,
Xenbase
Jiao,
A simple and sensitive antigen retrieval method for free-floating and slide-mounted tissue sections.
1999,
Pubmed
Johnson,
NMR View: A computer program for the visualization and analysis of NMR data.
1994,
Pubmed
Jones,
Improved methods for building protein models in electron density maps and the location of errors in these models.
1991,
Pubmed
Kaneko,
Identification and characterization of novel human Ca(v)2.2 (alpha 1B) calcium channel variants lacking the synaptic protein interaction site.
2002,
Pubmed
Kim,
Ca2+-dependent and -independent interactions of the isoforms of the alpha1A subunit of brain Ca2+ channels with presynaptic SNARE proteins.
1997,
Pubmed
Lipscombe,
Neuronal proteins custom designed by alternative splicing.
2005,
Pubmed
Opatowsky,
Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain.
2004,
Pubmed
Sakurai,
Biochemical properties and subcellular distribution of the BI and rbA isoforms of alpha 1A subunits of brain calcium channels.
1996,
Pubmed
Sutton,
Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.
1995,
Pubmed
Takahashi,
Distinctive modulatory effects of five human auxiliary beta2 subunit splice variants on L-type calcium channel gating.
2003,
Pubmed
Van Petegem,
Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.
2004,
Pubmed
Vendel,
Solution structure of the N-terminal A domain of the human voltage-gated Ca2+channel beta4a subunit.
2006,
Pubmed
Weiss,
The calcium channel beta4a subunit: a scaffolding protein between voltage-gated calcium channel and presynaptic vesicle-release machinery?
2006,
Pubmed
White,
Protein classification by stochastic modeling and optimal filtering of amino-acid sequences.
1994,
Pubmed
Yasuda,
Overexpressed Ca(v)beta3 inhibits N-type (Cav2.2) calcium channel currents through a hyperpolarizing shift of ultra-slow and closed-state inactivation.
2004,
Pubmed
,
Xenbase
Zamponi,
Regulation of presynaptic calcium channels by synaptic proteins.
2003,
Pubmed
Zhong,
Reciprocal regulation of P/Q-type Ca2+ channels by SNAP-25, syntaxin and synaptotagmin.
1999,
Pubmed