PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling
PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling
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DOI：
10.3390/ijms16059134
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Ying Liu
中科院分区：
文献类型：
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作者：
Ming Li;Fenghe Niu;Xilin Zhu;Xiaopan Wu;Ning Shen;Xiaozhong Peng;Ying Liu
Paroxysmal kinesigenic choreoathetosis (PKC) is an inherited disease of the nervous system. We previously identified PRRT2 as the causative gene of PKC. However, as little is known about the function of PRRT2, elucidating its function will benefit not only PKC studies, but also many other related disorders. Here, we reveal higher levels of glutamate in the plasma of PKC patients and the culture medium of neurons following knock-out Prrt2 expression. Using double immunostaining assays we confirm Prrt2 is located at the glutamatergic neurons in accordance with its function. Our co-immunoprecipitation assays reveal mutant PRRT2 interferes with SNAP25 and GRIA1 interactions, respectively. Furthermore, using live-labeling techniques, we confirmed co-transfection with mutant PRRT2 caused an increase in GRIA1 distribution on the cell surface. Therefore, our results suggest that mutant PRRT2, probably through its weakened interaction with SNAP25, affects glutamate signaling and glutamate receptor activity, resulting in the increase of glutamate release and subsequent neuronal hyperexcitability.
