Role of Aberrant Spontaneous Neurotransmission in SNAP25-Associated Encephalopathies
| Autor: | Lisa M. Monteggia, Rong Sun, Ok-Ho Shin, Pei-Yi Lin, K Ian White, Baris Alten, Qiangjun Zhou, Axel T. Brunger, Ege T. Kavalali, Luis Esquivies, Wendy K. Chung |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Adolescent Synaptosomal-Associated Protein 25 Synaptobrevin Mice Transgenic Haploinsufficiency Neurotransmission Biology Synaptic Transmission Synaptotagmin 1 Protein Structure Secondary Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Syntaxin Animals Humans Amino Acid Sequence Neurotransmitter Receptor Child Cells Cultured Mice Knockout Brain Diseases General Neuroscience SNAP25 Phenotype Rats 030104 developmental biology HEK293 Cells chemistry Child Preschool Female Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuron. 109(1) |
| ISSN: | 1097-4199 |
| Popis: | SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) complex, composed of synaptobrevin, syntaxin, and SNAP25, forms the essential fusion machinery for neurotransmitter release. Recent studies have reported several mutations in the gene encoding SNAP25 as a causative factor for developmental and epileptic encephalopathies of infancy and childhood with diverse clinical manifestations. However, it remains unclear how SNAP25 mutations give rise to these disorders. Here, we show that although structurally clustered mutations in SNAP25 give rise to related synaptic transmission phenotypes, specific alterations in spontaneous neurotransmitter release are a key factor to account for disease heterogeneity. Importantly, we identified a single mutation that augments spontaneous release without altering evoked release, suggesting that aberrant spontaneous release is sufficient to cause disease in humans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|