ArticleThe Journal of physiology2014
Syntaxin-binding domain of Kv2.1 is essential for the expression of apoptotic K+ currents.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Non-conducting functions of potassium channels in cancer and neurological disease.Current topics in membranes · 2023Review
- Regulation of neuronal excitation-transcription coupling by Kv2.1-induced clustering of somatic L-type CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Location, location, location: the organization and roles of potassium channels in mammalian motoneurons.The Journal of physiology · 2021Article
- Lessons from Recent Advances in Ischemic Stroke Management and Targeting Kv2.1 for Neuroprotection.International journal of molecular sciences · 2020Review
- Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels.Science advances · 2020Article
- The Redox Biology of Excitotoxic Processes: The NMDA Receptor, TOPA Quinone, and the Oxidative Liberation of Intracellular Zinc.Frontiers in neuroscience · 2020Review
- Voltage-Gated Potassium Channels as Regulators of Cell Death.Frontiers in cell and developmental biology · 2020Review
- Defining the Kv2.1-syntaxin molecular interaction identifies a first-in-class small molecule neuroprotectant.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Molecular Neuroprotection Induced by Zinc-Dependent Expression of Hepatitis C-Derived Protein NS5A Targeting Kv2.1 Potassium Channels.The Journal of pharmacology and experimental therapeutics · 2018Article
- Disruption of KNeuroscience · 2017Article
- Targeting a Potassium Channel/Syntaxin Interaction Ameliorates Cell Death in Ischemic Stroke.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Kv5, Kv6, Kv8, and Kv9 subunits: No simple silent bystanders.The Journal of general physiology · 2016Review
- Induction of stable ER-plasma-membrane junctions by Kv2.1 potassium channels.Journal of cell science · 2015Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Intracellular signalling cascades triggered by oxidative injury can lead to upregulation of Kv2.1 K(+) channels at the plasma membrane of dying neurons. Membrane incorporation of new channels is necessary for enhanced K(+) efflux and a consequent reduction of intracellular K(+) that facilitates apoptosis. We showed previously that the observed increase in K(+) currents is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated process, and that the SNARE protein syntaxin binds directly to Kv2.1 channels. In the present study, we tested whether disrupting the interaction of Kv2.1 and syntaxin promoted the survival of cortical neurons following injury. Syntaxin is known to bind to Kv2.1 in a domain comprising amino acids 411-522 of the channel's cytoplasmic C terminus (C1a). Here we show that this domain is required for the apoptotic K(+) current enhancement. Moreover, expression of an isolated, Kv2.1-derived C1a peptide is sufficient to suppress the injury-induced increase in currents by interfering with Kv2.1/syntaxin binding. By subdividing the C1a peptide, we were able to localize the syntaxin binding site on Kv2.1 to the most plasma membrane-distal residues of C1a. Importantly, expression of this peptide segment in neurons prevented the apoptotic K(+) current enhancement and cell death following an oxidative insult, without greatly impairing baseline K(+) currents or normal electrical profiles of neurons. These results establish that binding of syntaxin to Kv2.1 is crucial for the manifestation of oxidant-induced apoptosis, and thereby reveal a potential new direction for therapeutic intervention in the treatment of neurodegenerative disorders.
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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.