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- Title
Deficiency of SCAMP5 leads to pediatric epilepsy and dysregulation of neurotransmitter release in the brain.
- Authors
Zhang, Dazhi; Yuan, Chao; Liu, Mengxue; Zhou, Xiaopei; Ge, Shunnan; Wang, Xuelian; Luo, Geng; Hou, Meiqi; Liu, Zhenxing; Wang, Qing K.; Wang, Xu; Li, Haohong; Tan, Yang; Jia, Weimin; Wang, Jiarui; Wu, Yanling; Wang, Ali; Yang, Xiaofei; Zhang, Xianqin
- Abstract
Secretory carrier membrane proteins (SCAMPs) play an important role in exocytosis in animals, but the precise function of SCAMPs in human disease is unknown. In this study, we identified a homozygous mutation, SCAMP5 R91W, in a Chinese consanguineous family with pediatric epilepsy and juvenile Parkinson's disease. Scamp5 R91W mutant knock-in mice showed typical early-onset epilepsy similar to that in humans. Single-neuron electrophysiological recordings showed that the R91W mutation significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) at a resting state and also increased the amplitude of evoked EPSCs. The R91W mutation affected the interaction between SCAMP5 and synaptotagmin 1 and may affect the function of the SNARE complex, the machinery required for vesicular trafficking and neurotransmitter release. Our work shows that dysfunction of SCAMP5 shifted the excitation/inhibition balance of the neuronal network in the brain, and the deficiency of SCAMP5 leads to pediatric epilepsy.
- Subjects
EPILEPSY; PARKINSON'S disease; CARRIER proteins
- Publication
Human Genetics, 2020, Vol 139, Issue 4, p545
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-020-02123-9