ArticleNeuron2014
Age-related homeostatic midchannel proteolysis of neuronal L-type voltage-gated Ca²⁺ channels.
Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
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- The ryanodine receptor mutational characteristics and its indication for cancer prognosis.Scientific reports · 2022Article
- HIV-Induced Hyperactivity of Striatal Neurons Is Associated with Dysfunction of Voltage-Gated Calcium and Potassium Channels at Middle Age.Membranes · 2022Article
- Small Molecules as Modulators of Voltage-Gated Calcium Channels in Neurological Disorders: State of the Art and Perspectives.Molecules (Basel, Switzerland) · 2022Review
- Proteolytic regulation of calcium channels - avoiding controversy.Faculty reviews · 2022Article
- Depolarization induces nociceptor sensitization by CaV1.2-mediated PKA-II activation.The Journal of cell biology · 2021Article
- Calpain fosters the hyperexcitability of motoneurons after spinal cord injury and leads to spasticity.eLife · 2019Article
- CaCell death & disease · 2019Article
- Estrogen receptor α promotes Cav1.2 ubiquitination and degradation in neuronal cells and in APP/PS1 mice.Aging cell · 2019Article
- Differential regulation of ion channels function by proteolysis.Biochimica et biophysica acta. Molecular cell research · 2018Review
- Protein phosphorylation maintains the normal function of cloned human CaThe Journal of general physiology · 2018Article
- The calcium-cancer signalling nexus.Nature reviews. Cancer · 2017Review
- Dynamic association of calcium channel subunits at the cellular membrane.Neurophotonics · 2016Article
- A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant.Neurobiology of disease · 2016Article
- Calcium Revisited: New Insights Into the Molecular Basis of Long-QT Syndrome.Circulation. Arrhythmia and electrophysiology · 2016Review
- JPH-2 interacts with Cai-handling proteins and ion channels in dyads: Contribution to premature ventricular contraction-induced cardiomyopathy.Heart rhythm · 2016Article
- Targeting voltage-gated calcium channels in neurological and psychiatric diseases.Nature reviews. Drug discovery · 2016Review
- Article
- Cell-type-specific tuning of Cav1.3 Ca(2+)-channels by a C-terminal automodulatory domain.Frontiers in cellular neuroscience · 2015Article
- Article
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9 authors at 2 institutions in 2 countries.
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Abstract
Neural circuitry and brain activity depend critically on proper function of voltage-gated calcium channels (VGCCs), whose activity must be tightly controlled. We show that the main body of the pore-forming α1 subunit of neuronal L-type VGCCs, Cav1.2, is proteolytically cleaved, resulting in Cav1.2 fragment channels that separate but remain on the plasma membrane. This "midchannel" proteolysis is regulated by channel activity, involves the Ca(2+)-dependent protease calpain and the ubiquitin-proteasome system, and causes attenuation and biophysical alterations of VGCC currents. Recombinant Cav1.2 fragment channels mimicking the products of midchannel proteolysis do not form active channels on their own but, when properly paired, produce currents with distinct biophysical properties. Midchannel proteolysis increases dramatically with age and can be attenuated with an L-type VGCC blocker in vivo. Midchannel proteolysis represents a novel form of homeostatic negative-feedback processing of VGCCs that could profoundly affect neuronal excitability, neurotransmission, neuroprotection, and calcium signaling in physiological and disease states.
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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.