ArticleNature genetics2014
Ionic leakage underlies a gain-of-function effect of dominant disease mutations affecting diverse P-type ATPases.
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- ATP1A3-related neurological disorders: updated insights into clinical heterogeneity, molecular mechanisms and precision therapeutics.Neurogenetics · 2026Review
- ATP1A3 regulates protein synthesis for mitochondrial stability under heat stress.Disease models & mechanisms · 2024Article
- Cation leak through the ATP1A3 pump causes spasticity and intellectual disability.Brain : a journal of neurology · 2023Article
- Temperature instability of a mutation at a multidomain junction in Na,K-ATPase isoform ATP1A3 (p.Arg756His) produces a fever-induced neurological syndrome.The Journal of biological chemistry · 2023Article
- Article
- Restoration of Sarco/Endoplasmic Reticulum CaFrontiers in pharmacology · 2022Article
- Early role for a NaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Neural shutdown under stress: an evolutionary perspective on spreading depolarization.Journal of neurophysiology · 2020Review
- Primary Active CaCold Spring Harbor perspectives in biology · 2020Review
- Characterization of Hailey-Hailey Disease-mutants in presence and absence of wild type SPCA1 using Saccharomyces cerevisiae as model organism.Scientific reports · 2019Article
- Genotype-structure-phenotype relationships diverge in paralogsNeurology. Genetics · 2019Review
- Functional consequences of the CAPOS mutation E818K of NaThe Journal of biological chemistry · 2019Article
- Fever-related ataxia: a case report of CAPOS syndrome.Cerebellum & ataxias · 2019Article
- SERCA is critical to control the Bowditch effect in the heart.Scientific reports · 2018Article
- Pathways to neurodegeneration: lessons learnt from unbiased genetic screens inJournal of genetics · 2018Review
- Novel pregnancy-triggered episodes of CAPOS syndrome.American journal of medical genetics. Part A · 2018Review
- Structure/activity relationship of thapsigargin inhibition on the purified Golgi/secretory pathway CaThe Journal of biological chemistry · 2017Article
- ATP1A3 Mutation in Adult Rapid-Onset Ataxia.PloS one · 2016Article
- Single Enzyme Experiments Reveal a Long-Lifetime Proton Leak State in a Heme-Copper Oxidase.Journal of the American Chemical Society · 2015Article
- Distinct neurological disorders with ATP1A3 mutations.The Lancet. Neurology · 2014Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type II P-type ATPases (PAIIs) constitute a family of conserved proteins that actively generate ionic gradients across membranes. Mutations in genes encoding PAIIs can cause heritable dominant diseases, with suggested etiology of haploinsufficiency. Using a Drosophila melanogaster genetic screen, we identified a dominant mutation altering the PAII member sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA). This mutation conferred temperature-sensitive uncoordination in a gain-of-function manner. We established that this gain-of-function phenotype is linked to dominant disease-causing mutations affecting various human PAIIs. We further found that heterologous expression of mutant PAIIs elicited ion leakage that was exacerbated at elevated temperatures. Therefore, these dominant mutations result in ionic leakage and render PAIIs susceptible to deleterious effects from elevated temperatures. Accordingly, it was recently reported that missense mutations affecting the Na(+)/K(+) ATPase can elicit ionic leakage. We propose that ionic leakage is a pervasive gain-of-function mechanism that can underlie a variety of dominant PAII-related diseases.
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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.