| Literature DB >> 32020363 |
Dazhi Zhang1, Chao Yuan1,2, Mengxue Liu3, Xiaopei Zhou1, Shunnan Ge4, Xuelian Wang4, Geng Luo1, Meiqi Hou1, Zhenxing Liu1, Qing K Wang1,5, Xu Wang6,7, Haohong Li6,7, Yang Tan1, Weimin Jia1, Jiarui Wang1, Yanling Wu1, Ali Wang1, Xiaofei Yang3, Xianqin Zhang8.
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.Entities:
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Year: 2020 PMID： 32020363 DOI： 10.1007/s00439-020-02123-9
Source DB: PubMed Journal: Hum Genet ISSN： 0340-6717 Impact factor: 4.132