ALG13 participates in epileptogenesis via regulation of GABAA receptors in mouse models

Abstract ALG13 (asparagine-linked glycosylation 13) plays crucial roles in the process of N-linked glycosylation. Mutations of the ALG13 gene underlie congenital disorders of glycosylation type I (CDG-I), a rare human genetic disorder with defective glycosylation. Epilepsy is commonly observed in co...

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Published in:Cell death discovery 2020-09, Vol.6 (1), p.87-87, Article 87
Main Authors: Huo, Junming, Ren, Shuanglai, Gao, Peng, Wan, Ding, Rong, Shikuo, Li, Xinxiao, Liu, Shenhai, Xu, Siying, Sun, Kuisheng, Guo, Baorui, Wang, Peng, Yu, Baoli, Wu, Ji, Wang, Feng, Sun, Tao
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Language:English
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Summary:Abstract ALG13 (asparagine-linked glycosylation 13) plays crucial roles in the process of N-linked glycosylation. Mutations of the ALG13 gene underlie congenital disorders of glycosylation type I (CDG-I), a rare human genetic disorder with defective glycosylation. Epilepsy is commonly observed in congenital disorders of glycosylation type I (CDG-I). In our study, we found that about 20% of adult ALG13KO knockout mice display spontaneous seizures, which were identified in a simultaneous video and intracranial EEG recording. However, the mechanisms of ALG13 by which deficiency leads to epilepsy are unknown. Whole-cell patch-clamp recordings demonstrated that ALG13KO mice show a marked decrease in gamma-aminobutyric acid A receptor (GABA A R)-mediated inhibitory synaptic transmission. Furthermore, treatment with low-dose diazepam (a positive allosteric modulator of GABA A receptors), which enhances GABA A R function, also markedly ameliorates severity of epileptic seizures in ALG13KO mice. Moreover, ALG13 may influenced the expression of GABA A Rα2 membrane and total protein by changing transcription level of GABA A Rα2. Furthermore, protein interactions between ALG13 and GABA A Rα2 were observed in the cortex of wild-type mice. Overall, these results reveal that ALG13 may be involved in the occurrence of epilepsy through the regulation of GABA A R function, and may provide new insight into epilepsy prevention and treatment.
ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-020-00319-6