ArticleHuman genetics2009
Novel mutations affecting the Na, K ATPase alpha model complex neurological diseases and implicate the sodium pump in increased longevity.
Article in Human genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- ATP1A3-related neurological disorders: updated insights into clinical heterogeneity, molecular mechanisms and precision therapeutics.Neurogenetics · 2026Review
- Caenorhabditis elegans models of alternating hemiplegia of childhood have dominant neuromuscular junction defects.Disease models & mechanisms · 2026Article
- Article
- Na,K-ATPase Expression Can Be Limited Post-Transcriptionally: A Test of the Role of the Beta Subunit, and a Review of Evidence.International journal of molecular sciences · 2024Review
- eIF2α phosphorylation evokes dystonia-like movements with D2-receptor and cholinergic origin and abnormal neuronal connectivity.bioRxiv : the preprint server for biology · 2024Article
- Association between Decreased SGK1 and Increased Intestinal α-Synuclein in an MPTP Mouse Model of Parkinson's Disease.International journal of molecular sciences · 2023Article
- The role ofFrontiers in cellular neuroscience · 2023Review
- Genetically altered animal models for ATP1A3-related disorders.Disease models & mechanisms · 2021Article
- Factors in the disease severity of ATP1A3 mutations: Impairment, misfolding, and allele competition.Neurobiology of disease · 2019Article
- Article
- Adaptive substitutions underlying cardiac glycoside insensitivity in insects exhibit epistasis in vivo.eLife · 2019Article
- Potassium restriction boosts vacuolar acidity and extends lifespan in yeast.Experimental gerontology · 2019Article
- Caste-Specific Expression of NaNeotropical entomology · 2018Article
- Multidrug transporters and organic anion transporting polypeptides protect insects against the toxic effects of cardenolides.Insect biochemistry and molecular biology · 2017Article
- Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.Brain : a journal of neurology · 2015Article
- Genome-wide screen for modifiers of Na (+) /K (+) ATPase alleles identifies critical genetic loci.Molecular brain · 2014Article
- Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration.Experimental neurology · 2014Article
- Distinct neurological disorders with ATP1A3 mutations.The Lancet. Neurology · 2014Review
- The sodium-potassium pump is an information processing element in brain computation.Frontiers in physiology · 2014Article
- Emerging common molecular pathways for primary dystonia.Movement disorders : official journal of the Movement Disorder Society · 2013Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations affecting the Na(+), K(+) ATPase alpha subunit have been implicated in at least two distinct human diseases, rapid-onset dystonia Parkinsonism (RDP), and familial hemiplegic migraine (FHM). Over 40 mutations have been mapped to the human ATP1A2 and ATP1A3 genes and are known to result in RDP, FHM or a variant of FHM with neurological complications. To develop a genetically tractable model system for investigating the role of the Na(+), K(+) ATPase in neural pathologies we performed genetic screens in Drosophila melanogaster to isolate loss-of-function alleles affecting the Na(+), K(+) ATPase alpha subunit. Flies heterozygous for these mutations all exhibit reduced respiration, consistent with a loss-of-function in the major ATPase. However, these mutations do not affect all functions of the Na(+), K(+) ATPase alpha protein since embryos homozygous for these mutations have normal septate junction paracellular barrier function and tracheal morphology. Importantly, all of these mutations cause neurological phenotypes and, akin to the mutations that cause RDP and FHM, these new alleles are missense mutations. All of these alleles exhibit progressive stress-induced locomotor impairment suggesting neuromuscular dysfunction, yet neurodegeneration is observed in an allele-specific manner. Surprisingly, studies of longevity demonstrate that mild hypomorphic mutations in the sodium pump significantly improve longevity, which was verified using the Na(+), K(+) ATPase antagonist ouabain. The isolation and characterization of a series of new missense alleles of ATPalpha in Drosophila provides the foundation for further studies of these neurological diseases and the role of sodium pump impairment in animal longevity.
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