ArticlePloS one2011
The interaction between the first transmembrane domain and the thumb of ASIC1a is critical for its N-glycosylation and trafficking.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Acid-sensing ion channels in the vasculature: emerging roles in systemic and pulmonary circulations.Pflugers Archiv : European journal of physiology · 2026Review
- Mitochondrial acid-sensing ion channel 1a deficiency induces mitochondrial dysfunction in pulmonary arterial smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Enhanced glycolysis causes extracellular acidification and activates acid-sensing ion channel 1a in hypoxic pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Article
- The Role of ASIC1a in Epilepsy: A Potential Therapeutic Target.Current neuropharmacology · 2021Review
- Factors and Molecular Mechanisms Influencing the Protein Synthesis, Degradation and Membrane Trafficking of ASIC1a.Frontiers in cell and developmental biology · 2020Review
- Human ASIC1a mediates stronger acid-induced responses as compared with mouse ASIC1a.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Endomorphins potentiate acid-sensing ion channel currents and enhance the lactic acid-mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia.The Journal of physiology · 2017Article
- 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
- miR-149 reduces while let-7 elevates ASIC1a expression in vitro.International journal of physiology, pathophysiology and pharmacology · 2017Article
- Two di-leucine motifs regulate trafficking and function of mouse ASIC2a.Molecular brain · 2016Article
- ASIC subunit ratio and differential surface trafficking in the brain.Molecular brain · 2016Article
- ASICs and neuropeptides.Neuropharmacology · 2015Review
- Acid-sensing ion channels: trafficking and pathophysiology.Channels (Austin, Tex.) · 2014Review
- Three distinct motifs within the C-terminus of acid-sensing ion channel 1a regulate its surface trafficking.Neuroscience · 2013Article
- Acid-sensing ion channels: trafficking and synaptic function.Molecular brain · 2013Review
- Structure and activity of the acid-sensing ion channels.American journal of physiology. Cell physiology · 2012Review
- N-glycosylation of acid-sensing ion channel 1a regulates its trafficking and acidosis-induced spine remodeling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Inhibition of human acid-sensing ion channel 1b by zinc.International journal of physiology, pathophysiology and pharmacology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Acid-sensing ion channel-1a (ASIC1a), the primary proton receptor in the brain, contributes to multiple diseases including stroke, epilepsy and multiple sclerosis. Thus, a better understanding of its biogenesis will provide important insights into the regulation of ASIC1a in diseases. Interestingly, ASIC1a contains a large, yet well organized ectodomain, which suggests the hypothesis that correct formation of domain-domain interactions at the extracellular side is a key regulatory step for ASIC1a maturation and trafficking. We tested this hypothesis here by focusing on the interaction between the first transmembrane domain (TM1) and the thumb of ASIC1a, an interaction known to be critical in channel gating. We mutated Tyr71 and Trp287, two key residues involved in the TM1-thumb interaction in mouse ASIC1a, and found that both Y71G and W287G decreased synaptic targeting and surface expression of ASIC1a. These defects were likely due to altered folding; both mutants showed increased resistance to tryptic cleavage, suggesting a change in conformation. Moreover, both mutants lacked the maturation of N-linked glycans through mid to late Golgi. These data suggest that disrupting the interaction between TM1 and thumb alters ASIC1a folding, impedes its glycosylation and reduces its trafficking. Moreover, reducing the culture temperature, an approach commonly used to facilitate protein folding, increased ASIC1a glycosylation, surface expression, current density and slowed the rate of desensitization. These results suggest that correct folding of extracellular ectodomain plays a critical role in ASIC1a biogenesis and function.
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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.