Autism-associated SHANK3 haploinsufficiency causes I h channelopathy in human neurons
| Autor: | Fei Yi, Tamas Danko, Marius Wernig, Christopher Patzke, ChangHui Pak, Thomas C. Südhof, Salomé Calado Botelho |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Scaffold protein Autism Spectrum Disorder Chromosomes Human Pair 22 Action Potentials Chromosome Disorders Nerve Tissue Proteins Haploinsufficiency Biology Neurotransmission Synaptic Transmission Article Mice 03 medical and health sciences 0302 clinical medicine Channelopathy Postsynaptic potential Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels medicine Animals Humans Genetic Predisposition to Disease Cells Cultured Embryonic Stem Cells Mice Knockout Neurons Genetics Multidisciplinary Microfilament Proteins medicine.disease Phenotype Cell biology 030104 developmental biology Mutagenesis Synapses Excitatory postsynaptic potential Autism Channelopathies Chromosome Deletion Genetic Engineering Gene Deletion 030217 neurology & neurosurgery |
| Zdroj: | Science. 352 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.aaf2669 |
| Popis: | Faulty channels, not faulty synapses SHANK3 is a widely expressed scaffolding protein that is enriched in postsynaptic specializations. In mutant mice, SHANK3 mutations cause autism-like behavioral changes and exhibit alterations in synaptic transmission. Yi et al. produced human neurons lacking SHANK3 but not other genes that are also involved in the autism-like disease Phelan-McDermid syndrome. Instead of affecting synapses, SHANK3 mutations primarily caused a channelopathy, with the major phenotype consisting of a specific impairment of HCN channels. Chronic impairment of membrane currents through channelopathy could account for the phenotypes observed in Phelan-McDermid neurons, such as alterations in cognitive functions and the predisposition to epilepsy. Science , this issue p. 10.1126/science.aaf2669 |
| Databáze: | OpenAIRE |
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