ArticleThe Journal of biological chemistry2015
A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- Plasma membrane calcium ATPases and cerebellar pathology: what's the role in the ataxia?Biology direct · 2025Review
- Myelin-axon interface vulnerability in Alzheimer's disease revealed by subcellular proteomics and imaging of human and mouse brain.Nature neuroscience · 2025Article
- Phenotypical, genotypical and pathological characterization of the moonwalker mouse, a model of ataxia.Neurobiology of disease · 2024Article
- Whole exome sequencing revealed variants in four genes underlying X-linked intellectual disability in four Iranian families: novel deleterious variants and clinical features with the review of literature.BMC medical genomics · 2023Review
- The ataxia-linked E1081Q mutation affects the sub-plasma membrane CaCell death & disease · 2022Article
- De novo variants in ATP2B1 lead to neurodevelopmental delay.American journal of human genetics · 2022Article
- Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases.International journal of molecular sciences · 2021Review
- The de novo CACNA1A pathogenic variant Y1384C associated with hemiplegic migraine, early onset cerebellar atrophy and developmental delay leads to a loss of Cav2.1 channel function.Molecular brain · 2021Article
- The Role of TRP Channels and PMCA in Brain Disorders: Intracellular Calcium and pH Homeostasis.Frontiers in cell and developmental biology · 2021Review
- Rare CACNA1A mutations leading to congenital ataxia.Pflugers Archiv : European journal of physiology · 2020Review
- Construction and validation of a seven-gene signature for predicting overall survival in patients with kidney renal clear cell carcinoma via an integrated bioinformatics analysis.Animal cells and systems · 2020Article
- Identification of a likely pathogenic structural variation in theNPJ genomic medicine · 2020Article
- The Puzzling Role of Neuron-Specific PMCA Isoforms in the Aging Process.International journal of molecular sciences · 2019Review
- Structure of the human plasma membrane CaNature communications · 2018Article
- Evidence for a role of plasma membrane calcium pumps in neurodegenerative disease: Recent developments.Neuroscience letters · 2018Review
- The Exome Clinic and the role of medical genetics expertise in the interpretation of exome sequencing results.Genetics in medicine : official journal of the American College of Medical Genetics · 2017Article
- Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration.Scientific reports · 2017Article
- A positive feedback loop linking enhanced mGluR function and basal calcium in spinocerebellar ataxia type 2.eLife · 2017Article
- Dystonia in ATP2B3-associated X-linked spinocerebellar ataxia.Movement disorders : official journal of the Movement Disorder Society · 2016Article
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The particular importance of Ca(2+) signaling to neurons demands its precise regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca(2+) ATPase (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an important role in the regulation of neuronal Ca(2+). A genetic defect of the PMCA3 pump has been described in one family with X-linked congenital cerebellar ataxia. Here we describe a novel mutation in the ATP2B3 gene in a patient with global developmental delay, generalized hypotonia and cerebellar ataxia. The mutation (a R482H replacement) impairs the Ca(2+) ejection function of the pump. It reduces the ability of the pump expressed in model cells to control Ca(2+) transients generated by cell stimulation and impairs its Ca(2+) extrusion function under conditions of low resting cytosolic Ca(2+) as well. In silico analysis of the structural effect of the mutation suggests a reduced stabilization of the portion of the pump surrounding the mutated residue in the Ca(2+)-bound state. The patient also carries two missense mutations in LAMA1, encoding laminin subunit 1α. On the basis of the family pedigree of the patient, the presence of both PMCA3 and laminin subunit 1α mutations appears to be necessary for the development of the disease. Considering the observed defect in cellular Ca(2+) homeostasis and the previous finding that PMCAs act as digenic modulators in Ca(2+)-linked pathologies, the PMCA3 dysfunction along with LAMA1 mutations could act synergistically to cause the neurological phenotype.
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