ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Interaction via a key tryptophan in the I-II linker of N-type calcium channels is required for beta1 but not for palmitoylated beta2, implicating an additional binding site in the regulation of channel voltage-dependent properties.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 82 citations in OpenAlex.
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- How Postdoctoral Research in Paul Greengard's Laboratory Shaped My Scientific Career, Although I Never Did Another Phosphorylation Assay.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Disruption of the Key CaCell reports · 2019Article
- AAV-encoded CaGene therapy · 2019Article
- Modulation of CaBMC research notes · 2018Article
- Constitutive activity of the Ghrelin receptor reduces surface expression of voltage-gated CaJournal of cell science · 2017Article
- Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology.The Journal of physiology · 2016Review
- The CaVβ Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination.The Journal of biological chemistry · 2016Article
- Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders.Progress in neurobiology · 2015Review
- The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential.Pharmacological reviews · 2015Review
- A Polybasic Plasma Membrane Binding Motif in the I-II Linker Stabilizes Voltage-gated CaV1.2 Calcium Channel Function.The Journal of biological chemistry · 2015Article
- 14-3-3τ promotes surface expression of Cav2.2 (α1B) Ca2+ channels.The Journal of biological chemistry · 2015Article
- Functional exofacially tagged N-type calcium channels elucidate the interaction with auxiliary α2δ-1 subunits.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Fragile X mental retardation protein controls synaptic vesicle exocytosis by modulating N-type calcium channel density.Nature communications · 2014Article
- The inhibition of functional expression of calcium channels by prion protein demonstrates competition with α2δ for GPI-anchoring pathways.The Biochemical journal · 2014Article
- Ankyrin-B regulates Cav2.1 and Cav2.2 channel expression and targeting.The Journal of biological chemistry · 2014Article
- Regulation of Ca(V)2 calcium channels by G protein coupled receptors.Biochimica et biophysica acta · 2013Review
Corrections and comments
- Erratum issuedRichards, Mark S [corrected to Richards, Mark W]
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The CaVbeta subunits of voltage-gated calcium channels regulate these channels in several ways. Here we investigate the role of these auxiliary subunits in the expression of functional N-type channels at the plasma membrane and in the modulation by G-protein-coupled receptors of this neuronal channel. To do so, we mutated tryptophan 391 to an alanine within the alpha-interacting domain (AID) in the I-II linker of CaV2.2. We showed that the mutation W391 virtually abolishes the binding of CaVbeta1b and CaVbeta2a to the CaV2.2 I-II linker and strongly reduced current density and cell surface expression of both CaV2.2/alpha2delta-2/beta1b and/beta2a channels. When associated with CaVbeta1b, the W391A mutation also prevented the CaVbeta1b-mediated hyperpolarization of CaV2.2 channel activation and steady-state inactivation. However, the mutated CaV2.2W391A/beta1b channels were still inhibited to a similar extent by activation of the D2 dopamine receptor with the agonist quinpirole. Nevertheless, key hallmarks of G-protein modulation of N-type currents, such as slowed activation kinetics and prepulse facilitation, were not observed for the mutated channel. In contrast, CaVbeta2a was still able to completely modulate the biophysical properties of CaV2.2W391A channel and allow voltage-dependent G-protein modulation of CaV2.2W391A. Additional data suggest that the concentration of CaVbeta2a in the proximity of the channel is enhanced independently of its binding to the AID by its palmitoylation. This is essentially sufficient for all of the functional effects of CaVbeta2a, which may occur via a second lower-affinity binding site, except trafficking the channel to the plasma membrane, which requires interaction with the AID region.
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