ArticleProceedings of the National Academy of Sciences of the United States of America2014
Functional exofacially tagged N-type calcium channels elucidate the interaction with auxiliary α2δ-1 subunits.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- N-Type Ca Channel in Epileptic Syndromes and Epilepsy: A Systematic Review of Its Genetic Variants.International journal of molecular sciences · 2023Pooled it
- Role of the C-terminal domain in modifying pH-dependent regulation of CaChannels (Austin, Tex.) · 2025Article
- Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs.Open biology · 2025Review
- Unraveling the Role of α2δ-1 in Cerebral Hemorrhage: Calcium Overload, Endoplasmic Reticulum Stress, and Microglial Apoptosis.Brain and behavior · 2025Article
- The N-type calcium channel rises from the ashes.The Journal of clinical investigation · 2025Article
- Electrosome assembly: Structural insights from high voltage-activated calcium channel (CaV)-chaperone interactions.Biochemical Society transactions · 2025Review
- Regulatory Action of Calcium and Calcium Channels in Pain Pathways.International journal of biological sciences · 2025Review
- A biallelic mutation in CACNA2D2 associated with developmental and epileptic encephalopathy affects calcium channel-dependent as well as synaptic functions of αJournal of neurochemistry · 2025Article
- Structural biology of voltage-gated calcium channels.Channels (Austin, Tex.) · 2024Review
- Pregabalin produces analgesia in males but not females in an animal model of chronic widespread muscle pain.Pain reports · 2024Article
- Rat Sympathetic Neuron Calcium Channels Are Insensitive to Gabapentin.Pharmaceuticals (Basel, Switzerland) · 2024Article
- CaeLife · 2024Article
- Peptide and Peptidomimetic Inhibitors Targeting the Interaction of Collapsin Response Mediator Protein 2 with the N-Type Calcium Channel for Pain Relief.ACS pharmacology & translational science · 2024Review
- Functional remodeling of presynaptic voltage-gated calcium channels in superficial layers of the dorsal horn during neuropathic pain.iScience · 2024Article
- CabioRxiv : the preprint server for biology · 2024Article
- The Interplay Between Splicing of Two Exon Combinations Differentially Affects Membrane Targeting and Function of Human CaFunction (Oxford, England) · 2024Article
- The importance of cache domains in αChannels (Austin, Tex.) · 2023Article
- Chronic pregabalin treatment protects against spreading depolarization and alters hippocampal synaptic characteristics in a model of familial hemiplegic migraine-type 1.Molecular brain · 2023Article
- Active Zone Trafficking of CaV2/UNC-2 Channels Is Independent of β/CCB-1 and α2δ/UNC-36 Subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- EMC chaperone-CaNature · 2023Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
CaV1 and CaV2 voltage-gated calcium channels are associated with β and α2δ accessory subunits. However, examination of cell surface-associated CaV2 channels has been hampered by the lack of antibodies to cell surface-accessible epitopes and of functional exofacially tagged CaV2 channels. Here we report the development of fully functional CaV2.2 constructs containing inserted surface-accessible exofacial tags, which allow visualization of only those channels at the plasma membrane, in both a neuronal cell line and neurons. We first examined the effect of the auxiliary subunits. Although α2δ subunits copurify with CaV2 channels, it has recently been suggested that this interaction is easily disrupted and nonquantitative. We have now tested whether α2δ subunits are associated with these channels at the cell surface. We found that, whereas α2δ-1 is readily observed at the plasma membrane when expressed alone, it appears absent when coexpressed with CaV2.2/β1b, despite our finding that α2δ-1 increases plasma-membrane CaV2.2 expression. However, this was due to occlusion of the antigenic epitope by association with CaV2.2, as revealed by antigen retrieval; thus, our data provide evidence for a tight interaction between α2δ-1 and the α1 subunit at the plasma membrane. We further show that, although CaV2.2 cell-surface expression is reduced by gabapentin in the presence of wild-type α2δ-1 (but not a gabapentin-insensitive α2δ-1 mutant), the interaction between CaV2.2 and α2δ-1 is not disrupted by gabapentin. Altogether, these results demonstrate that CaV2.2 and α2δ-1 are intimately associated at the plasma membrane and allow us to infer a region of interaction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.