ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Molecular mechanism of constitutive endocytosis of Acid-sensing ion channel 1a and its protective function in acidosis-induced neuronal death.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Acid-sensing ion channels in ischemic stroke: amplifying and constraining neuronal injury in a phase-specific framework.Pflugers Archiv : European journal of physiology · 2026Review
- Blocking acid-sensing ion channel 1a attenuates bilirubin-induced ototoxicity in cochlear organotypic culture.Fundamental research · 2026Article
- The secreted protein PCYOX1L controls the surface expression of acid-sensing ion channel 1a.Science advances · 2025Article
- Regulation of acid-sensing ion channels by protein binding partners.Channels (Austin, Tex.) · 2021Article
- Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a.Neuroscience bulletin · 2021Article
- Acid-Sensing Ion Channels: Expression and Function in Resident and Infiltrating Immune Cells in the Central Nervous System.Frontiers in cellular neuroscience · 2021Review
- Hydrogen Sulfide Upregulates Acid-sensing Ion ChannelsFunction (Oxford, England) · 2021Article
- The Role of ASIC1a in Epilepsy: A Potential Therapeutic Target.Current neuropharmacology · 2021Review
- Disruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis.Nature communications · 2020Article
- Factors and Molecular Mechanisms Influencing the Protein Synthesis, Degradation and Membrane Trafficking of ASIC1a.Frontiers in cell and developmental biology · 2020Review
- Protein Kinase C Lambda Mediates Acid-Sensing Ion Channel 1a-Dependent Cortical Synaptic Plasticity and Pain Hypersensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Acid-sensing ion channels: dual function proteins for chemo-sensing and mechano-sensing.Journal of biomedical science · 2018Review
- Naked mole-rat cortical neurons are resistant to acid-induced cell death.Molecular brain · 2018Article
- Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- ASIC1 promotes differentiation of neuroblastoma by negatively regulating Notch signaling pathway.Oncotarget · 2017Article
- ASIC1a mediates the drug resistance of human hepatocellular carcinoma via the CaLaboratory investigation; a journal of technical methods and pathology · 2017Article
- Acid-Sensing Ion Channels as Potential Therapeutic Targets in Neurodegeneration and Neuroinflammation.Mediators of inflammation · 2017Review
- The Protein Tyrosine Kinase Inhibitor Tyrphostin 23 Strongly Accelerates Glycolytic Lactate Production in Cultured Primary Astrocytes.Neurochemical research · 2016Article
- Neurorestoration after stroke.Neurosurgical focus · 2016Review
- Altered Expression Pattern of Acid-Sensing Ion Channel Isoforms in Piriform Cortex After Seizures.Molecular neurobiology · 2016Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Acid-sensing ion channels (ASICs) are proton-gated cation channels widely expressed in the peripheral and CNSs, which critically contribute to a variety of pathophysiological conditions that involve tissue acidosis, such as ischemic stroke and epileptic seizures. However, the trafficking mechanisms of ASICs and the related proteins remain largely unknown. Here, we demonstrate that ASIC1a, the main ASIC subunit in the brain, undergoes constitutive endocytosis in a clathrin- and dynamin-dependent manner in both mouse cortical neurons and heterologous cell cultures. The endocytosis of ASIC1a was inhibited by either the small molecular inhibitor tyrphostin A23 or knockdown of the core subunit of adaptor protein 2 (AP2) μ2 using RNA interference, supporting a clathrin-dependent endocytosis of ASIC1a. In addition, the internalization of ASIC1a was blocked by dominant-negative dynamin1 mutation K44A and the small molecular inhibitor dynasore, suggesting that it is also dynamin-dependent. We show that the membrane-proximal residues (465)LCRRG(469) at the cytoplasmic C terminus of ASIC1a are critical for interaction with the endogenous adaptor protein complex and inhibition of ASIC1a internalization strongly exacerbated acidosis-induced death of cortical neurons from wild-type but not ASIC1a knock-out mice. Together, these results reveal the molecular mechanism of ASIC1a internalization and suggest the importance of endocytic pathway in functional regulation of ASIC1a channels as well as neuronal damages mediated by these channels during neurodegeneration.
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