一个新突触蛋白PRRT2的研究进展

Research Progress of a Novel Synaptic Protein PRRT2

近几年的研究表明,PRRT2基因是PKD、BFIS、ICCA、偏头痛、发作性共济失调、热性惊厥、癫痫等多种发作性疾病的致病基因。进一步功能研究发现,PRRT2蛋白主要富集于大脑神经元的突触前膜,与SNARE复合物蛋白相互作用,参与调节突触功能并促进突触囊泡的胞吐过程,因此提出PRRT2是一个新的突触蛋白。更重要的是,突变型PRRT2蛋白的表达水平低于野生型,并且膜定位发生改变,从而使该蛋白的功能缺失。由此推测,由于患者中PRRT2蛋白单倍剂量不足而导致神经递质释放失调,可能是PRRT2相关疾病的致病机制。文章主要就近年来对PRRT2的研究进展进行了综述。

Recent studies have shown that PRRT2 is the causative gene of PKD,BFIS,ICCA,migraine,episodic ataxia,febrile seizures and epilepsy. Further functional studies have found that PRRT2 protein is mainly enriched in presynaptic membrane of neurons,where it interacts with SNARE proteins,and is involved in mediating synaptic function and promoting the exocytosis of synaptic vesicles. More importantly,most of the expression level of mutant PRRT2 protein is lower than that of wild type,and the subcellular localization of mutant PRRT2 is abnormal,and losting membrane targeting,all of these caused the loss of function of PRRT2. It is speculated that due to the haploinsufficiency of PRRT2 protein in patients leads to neurotransmitter release disorders,which may be the pathogenesis of PRRT2-related diseases. This paper reviews the progress of research on PRRT2 in recent years.