ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
A destructive interaction mechanism accounts for dominant-negative effects of misfolded mutants of voltage-gated calcium channels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 81 citations in OpenAlex.
- Pin1 promotes human CaCell communication and signaling : CCS · 2024Article
- The T-type calcium channelosome.Pflugers Archiv : European journal of physiology · 2024Review
- The good company of T-type calcium channels : Commentary on: "T-type calcium channelosome," a review by N. Weiss and G. W. Zamponi.Pflugers Archiv : European journal of physiology · 2024Article
- The life cycle of voltage-gated CaNeuronal signaling · 2021Review
- Voltage-Gated CaFrontiers in synaptic neuroscience · 2021Review
- A sleep modulated Channelopathy: a novel CACNA1A pathogenic variant identified in episodic Ataxia type 2 and a potential link to sleep alleviated migraine.BMC neurology · 2019Article
- Gain-of-function mutations in the UNC-2/CaV2α channel lead to excitation-dominant synaptic transmission ineLife · 2019Article
- Zebrafish as a Model System for the Study of Severe CaFrontiers in molecular neuroscience · 2019Review
- Alternative Splicing at N Terminus and Domain I Modulates CaBiophysical journal · 2018Article
- From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying Neuropsychiatric Symptoms.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
- Mutation Spectrum in the CACNA1A Gene in 49 Patients with Episodic Ataxia.Scientific reports · 2017Article
- Ubiquitin Ligase RNF138 Promotes Episodic Ataxia Type 2-Associated Aberrant Degradation of Human CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Aberrant Splicing Promotes Proteasomal Degradation of L-type CaScientific reports · 2016Article
- A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant.Neurobiology of disease · 2016Article
- BESTROPHIN1 mutations cause defective chloride conductance in patient stem cell-derived RPE.Human molecular genetics · 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
- Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop.The Journal of biological chemistry · 2015Article
- De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay.American journal of human genetics · 2015Article
- The first knockin mouse model of episodic ataxia type 2.Experimental neurology · 2014Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Channelopathies are often linked to defective protein folding and trafficking. Among them, the calcium channelopathy episodic ataxia type-2 (EA2) is an autosomal dominant disorder related to mutations in the pore-forming Ca(v)2.1 subunit of P/Q-type calcium channels. Although EA2 is linked to loss of Ca(v)2.1 channel activity, the molecular mechanism underlying dominant inheritance remains unclear. Here, we show that EA2 mutants as well as a truncated form (D(I-II)) of the Ca(v)3.2 subunit of T-type calcium channel are misfolded, retained in the endoplasmic reticulum, and subject to proteasomal degradation. Pulse-chase experiments revealed that misfolded mutants bind to nascent wild-type Ca(v) subunits and induce their subsequent degradation, thereby abolishing channel activity. We conclude that this destructive interaction mechanism promoted by Ca(v) mutants is likely to occur in EA2 and in other inherited dominant channelopathies.
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Registered trials
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.