ArticlePloS one2008
Orientation of the calcium channel beta relative to the alpha(1)2.2 subunit is critical for its regulation of channel activity.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- CaMolecular brain · 2022Article
- Article
- β-adrenergic-mediated dynamic augmentation of sarcolemmal CaThe Journal of physiology · 2019Article
- Variants in Ion Channel Genes Link Phenotypic Features of Bipolar Illness to Specific Neurobiological Process Domains.Molecular neuropsychiatry · 2015Review
- Cav3 T-type channels: regulators for gating, membrane expression, and cation selectivity.Pflugers Archiv : European journal of physiology · 2014Review
- Ins and outs of T-channel structure function.Pflugers Archiv : European journal of physiology · 2014Review
- Article
- Structure and function of the β subunit of voltage-gated Ca²⁺ channels.Biochimica et biophysica acta · 2013Review
- Structural flexibility of CaV1.2 and CaV2.2 I-II proximal linker fragments in solution.Biophysical journal · 2013Article
- Stable incorporation versus dynamic exchange of β subunits in a native Ca2+ channel complex.Journal of cell science · 2013Article
- The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Mechanism of auxiliary β-subunit-mediated membrane targeting of L-type (Ca(V)1.2) channels.The Journal of physiology · 2011Article
- Timothy mutation disrupts the link between activation and inactivation in Ca(V)1.2 protein.The Journal of biological chemistry · 2011Article
- Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.The EMBO journal · 2010Article
- The ß subunit of voltage-gated Ca2+ channels.Physiological reviews · 2010Review
- Direct inhibition of P/Q-type voltage-gated Ca2+ channels by Gem does not require a direct Gem/Cavbeta interaction.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Molecular endpoints of Ca2+/calmodulin- and voltage-dependent inactivation of Ca(v)1.3 channels.The Journal of general physiology · 2010Article
- Structural determinants of the high affinity extracellular zinc binding site on Cav3.2 T-type calcium channels.The Journal of biological chemistry · 2010Article
- Orientation of palmitoylated CaVbeta2a relative to CaV2.2 is critical for slow pathway modulation of N-type Ca2+ current by tachykinin receptor activation.The Journal of general physiology · 2009Article
- An oily competition: role of beta subunit palmitoylation for Ca2+ channel modulation by fatty acids.The Journal of general physiology · 2009Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Ca(v)beta subunits of high voltage-activated Ca(2+) channels control the trafficking and biophysical properties of the alpha(1) subunit. The Ca(v)beta-alpha(1) interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that betas regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the alpha-interaction domain (AID) be a rigid structure. METHODOLOGY/PRINCIPAL
findingsThe present study tests this hypothesis by altering the flexibility and orientation of this region in alpha(1)2.2, then testing for Ca(v)beta regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6). This mutation abolished beta2a and beta3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of beta2a to produce non-inactivating currents. Orientation of Ca(v)beta with respect to alpha(1)2.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively). Again, the ability of Ca(v)beta subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Ca(v)beta subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms beta-sheet. The orientation of beta with respect to alpha was confirmed by the bimolecular fluorescence complementation assay. CONCLUSIONS/SIGNIFICANCE: These results show that the orientation of the Ca(v)beta subunit relative to the alpha(1)2.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(v)beta to regulate channel activity.
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