ArticleHuman molecular genetics2017
Biophysical and functional characterization of hippocalcin mutants responsible for human dystonia.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 41 citations in OpenAlex.
- Hippocalcin Regulates NMDA Receptor Function and Neuronal Activity Through Elavl3 in Mouse Hippocampal Neural Precursor Cells.International journal of molecular sciences · 2026Article
- Chemoproteomics identifies protein ligands for monoacylglycerol lipids.Communications chemistry · 2025Article
- Real-Time, Non-Invasive Monitoring of Neuronal Differentiation Using Intein-Enabled Fluorescence Signal Translocation in Genetically Encoded Stem Cell-Based Biosensors.Advanced functional materials · 2024Article
- Protective effect of Tat fused HPCA protein on neuronal cell death caused by ischemic injury.Heliyon · 2024Article
- Childhood-Onset Choreo-Dystonia Due to a Recurrent Novel Homozygous NonsenseMovement disorders clinical practice · 2023Review
- Benign Hereditary Chorea as a Manifestation of HPCA Mutation.Movement disorders clinical practice · 2023Article
- Zinc Modulation of Neuronal Calcium Sensor Proteins: Three Modes of Interaction with Different Structural Outcomes.Biomolecules · 2022Article
- Genetic Dystonias: Update on Classification and New Genetic Discoveries.Current neurology and neuroscience reports · 2021Review
- Reduced Expression of GABAFrontiers in cell and developmental biology · 2021Article
- Neuronal Plasticity: Neuronal Organization is Associated with Neurological Disorders.Journal of molecular neuroscience : MN · 2020Review
- Serum calcium, magnesium, phosphorus, and vitamin D in benign essential blepharospasm.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2020Article
- PINK1/Parkin Mediated Mitophagy, CaInternational journal of molecular sciences · 2020Review
- Calcium Sensors in Neuronal Function and Dysfunction.Cold Spring Harbor perspectives in biology · 2019Review
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dystonia is a neurological movement disorder that forces the body into twisting, repetitive movements or sometimes painful abnormal postures. With the advent of next-generation sequencing technologies, the homozygous mutations T71N and A190T in the neuronal calcium sensor (NCS) hippocalcin were identified as the genetic cause of primary isolated dystonia (DYT2 dystonia). However, the effect of these mutations on the physiological role of hippocalcin has not yet been elucidated. Using a multidisciplinary approach, we demonstrated that hippocalcin oligomerises in a calcium-dependent manner and binds to voltage-gated calcium channels. Mutations T71N and A190T in hippocalcin did not affect stability, calcium-binding affinity or translocation to cellular membranes (Ca2+/myristoyl switch). We obtained the first crystal structure of hippocalcin and alignment with other NCS proteins showed significant variability in the orientation of the C-terminal part of the molecule, the region expected to be important for target binding. We demonstrated that the disease-causing mutations did not affect the structure of the protein, however both mutants showed a defect in oligomerisation. In addition, we observed an increased calcium influx in KCl-depolarised cells expressing mutated hippocalcin, mostly driven by N-type voltage-gated calcium channels. Our data demonstrate that the dystonia-causing mutations strongly affect hippocalcin cellular functions which suggest a central role for perturbed calcium signalling in DYT2 dystonia.
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