ArticleNature2010
Neurological disease mutations compromise a C-terminal ion pathway in the Na(+)/K(+)-ATPase.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 140 citations in OpenAlex.
- On the mechanism of hypomagnesemia with treatment-resistant seizures caused by variants of the Na+,K+-ATPase α1 subunit (ATP1A1).The Journal of general physiology · 2026Article
- Active conformations of neuronal NaNature communications · 2026Article
- Distinct transport cycle and lipid regulation of a MgResearch square · 2026Article
- Abnormal neurovascular coupling induces glymphatic dysfunction in a mouse model of familial hemiplegic migraine type 2.The journal of headache and pain · 2025Article
- The Quaternary Structure of the Sodium Pump Regulatory Complex Is Altered by Mutations of a Site Associated with Familial Hemiplegic Migraine.Molecular neurobiology · 2025Article
- Multistate Kinetic Model of the Sodium-Potassium ATPase.The journal of physical chemistry. B · 2025Article
- The Unified Theory of Neurodegeneration Pathogenesis Based on Axon Deamidation.International journal of molecular sciences · 2025Review
- Synthetic Naphthoquinone Inhibits Herpes Simplex Virus Type-1 Replication Targeting NaACS omega · 2024Article
- A Na pump with reduced stoichiometry is up-regulated by brine shrimp in extreme salinities.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structure and function of HNature communications · 2022Article
- The role of NaCNS neuroscience & therapeutics · 2022Review
- Disease mutations of human α3 NaPNAS nexus · 2022Article
- The NaThe Journal of biological chemistry · 2022Article
- Diseases caused by mutations in the NaAmerican journal of physiology. Cell physiology · 2021Review
- The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair.International journal of molecular sciences · 2021Review
- Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations.Epilepsy & behavior : E&B · 2021Article
- Transient Electrical Currents Mediated by the NaBiophysical journal · 2020Review
- Cyclosporine A inhibits MRTF-SRF signaling through NaFASEB bioAdvances · 2019Article
- Article
- Functional consequences of the CAPOS mutation E818K of NaThe Journal of biological chemistry · 2019Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Na(+)/K(+)-ATPase pumps three sodium ions out of and two potassium ions into the cell for each ATP molecule that is split, thereby generating the chemical and electrical gradients across the plasma membrane that are essential in, for example, signalling, secondary transport and volume regulation in animal cells. Crystal structures of the potassium-bound form of the pump revealed an intimate docking of the alpha-subunit carboxy terminus at the transmembrane domain. Here we show that this element is a key regulator of a previously unrecognized ion pathway. Current models of P-type ATPases operate with a single ion conduit through the pump, but our data suggest an additional pathway in the Na(+)/K(+)-ATPase between the ion-binding sites and the cytoplasm. The C-terminal pathway allows a cytoplasmic proton to enter and stabilize site III when empty in the potassium-bound state, and when potassium is released the proton will also return to the cytoplasm, thus allowing an overall asymmetric stoichiometry of the transported ions. The C terminus controls the gate to the pathway. Its structure is crucial for pump function, as demonstrated by at least eight mutations in the region that cause severe neurological diseases. This novel model for ion transport by the Na(+)/K(+)-ATPase is established by electrophysiological studies of C-terminal mutations in familial hemiplegic migraine 2 (FHM2) and is further substantiated by molecular dynamics simulations. A similar ion regulation is likely to apply to the H(+)/K(+)-ATPase and the Ca(2+)-ATPase.
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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.