Author Correction: Aberrant activity of mitochondrial NCLX is linked to impaired synaptic transmission and is associated with mental retardation
| Autor: | Fabiana Perocchi, Ivana Savic, Steffen Leiz, Tomer Katoshevsky, Cornelia Daumer-Haas, Daniel Gitler, Yael Amitai, Essam A. Assali, Israel Sekler, Ohad Stoler, Marko Kostic, Holger Prokisch, Alexandra Stavsky, Ilya A. Fleidervish |
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| Rok vydání: | 2021 |
| Předmět: |
Male
QH301-705.5 Long-Term Potentiation Presynaptic Terminals Medicine (miscellaneous) In Vitro Techniques Biology Neurotransmission Hippocampus Synaptic Transmission Sodium-Calcium Exchanger General Biochemistry Genetics and Molecular Biology Mitochondrial Proteins Mice Text mining Intellectual Disability Animals Humans Point Mutation Amino Acid Sequence Calcium Signaling Biology (General) Author Correction Mice Knockout Neurons Neuronal Plasticity business.industry Calcium signalling Cellular neuroscience Mitochondria Pedigree Mice Inbred C57BL Amino Acid Substitution Female Cardiomyopathies General Agricultural and Biological Sciences business Neuroscience |
| Zdroj: | Communications Biology, Vol 4, Iss 1, Pp 1-1 (2021) Communications Biology |
| ISSN: | 2399-3642 |
| DOI: | 10.1038/s42003-021-02312-w |
| Popis: | Calcium dynamics control synaptic transmission. Calcium triggers synaptic vesicle fusion, determines release probability, modulates vesicle recycling, participates in long-term plasticity and regulates cellular metabolism. Mitochondria, the main source of cellular energy, serve as calcium signaling hubs. Mitochondrial calcium transients are primarily determined by the balance between calcium influx, mediated by the mitochondrial calcium uniporter (MCU), and calcium efflux through the sodium/lithium/calcium exchanger (NCLX). We identified a human recessive missense SLC8B1 variant that impairs NCLX activity and is associated with severe mental retardation. On this basis, we examined the effect of deleting NCLX in mice on mitochondrial and synaptic calcium homeostasis, synaptic activity, and plasticity. Neuronal mitochondria exhibited basal calcium overload, membrane depolarization, and a reduction in the amplitude and rate of calcium influx and efflux. We observed smaller cytoplasmic calcium transients in the presynaptic terminals of NCLX-KO neurons, leading to a lower probability of release and weaker transmission. In agreement, synaptic facilitation in NCLX-KO hippocampal slices was enhanced. Importantly, deletion of NCLX abolished long term potentiation of Schaffer collateral synapses. Our results show that NCLX controls presynaptic calcium transients that are crucial for defining synaptic strength as well as short- and long-term plasticity, key elements of learning and memory processes. |
| Databáze: | OpenAIRE |
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