PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum

• DOI: 10.1038/cr.2017.128
• Publication Date: 2017-10-20T10:59:13Z
• Authors: Guo-He Tan; Yuan-Yuan Liu; Lu Wang; Kui Li; Ze-Qiang Zhang; Hong-Fu Li; Zhong-Fei Yang; Yang Li; Dan Li; Ming-Yue Wu; Chun-Lei Yu; Juan-Juan Long; Ren-Chao Chen; Li-Xi Li; Lu-Ping Yin; Ji-Wei Liu; Xue-Wen Cheng; Qi Shen; You-Sheng Shu; Kenji Sakimura; Lu-Jian Liao; Zhi-Ying Wu; Zhi-Qi Xiong
• Keywords: Paroxysmal dyskinesia

Mutations in the proline-rich transmembrane protein 2 (PRRT2) are associated with paroxysmal kinesigenic dyskinesia (PKD) and several other neurological diseases, but PRRT2 function pathogenic mechanisms remain largely obscure. Here we show that is a presynaptic interacts components of SNARE complex downregulates its formation. Loss-of-function mutant mice showed PKD-like phenotypes triggered by generalized seizures, hyperthermia, or optogenetic stimulation cerebellum. Mutant specific deletion cerebellar granule cells (GCs) recapitulate behavioral seen Prrt2-null mice. Furthermore, recording made slices GCs results transient elevation followed suppression Purkinje cell firing. The anticonvulsant drug carbamazepine used PKD treatment also relieved behaviors Together, our findings identify as novel regulator provide circuit mechanism underlying PRRT2-related behaviors.