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Int. J. Mol. Sci. 2015, 16(5), 9134-9151; doi:10.3390/ijms16059134

PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
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Academic Editor: Sabrina Angelini
Received: 6 March 2015 / Revised: 10 April 2015 / Accepted: 13 April 2015 / Published: 23 April 2015
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)
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Abstract

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. View Full-Text
Keywords: PRRT2; glutamate; SNAP25; GRIA1 PRRT2; glutamate; SNAP25; GRIA1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, M.; Niu, F.; Zhu, X.; Wu, X.; Shen, N.; Peng, X.; Liu, Y. PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling. Int. J. Mol. Sci. 2015, 16, 9134-9151.

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