Investigating the Functions of RME8 in Parkinson's Disease

摘要 DNAJC蛋白家族(DNAJC5-26)是近年来引起人们关注的辅伴蛋白的一个亚类。 用于识别与帕金森症有关的突变。在这里，我们重点介绍DNAJC13，它编码 受体介导的内吞作用8(RME8)，一种促进膜循环和货物分拣的辅助伴侣 内吞的蛋白质。RME8主要定位于早期的内吞体膜，作为一种 蛋白质和膜交通的总机。在帕金森病患者中，RME8的不同突变 然而，需要更多的证据来理解RME8在帕金森病中的作用 活着。我们的建议将系统地评估小说中1)行为、2)病理和3)细胞变化 RME8小鼠模型，作为年龄的函数，并确定它们是否复制PD特征。我们的目标是定义 RME8在帕金森病中的作用及帕金森病的治疗干预要点

SUMMARY The DNAJC protein family (DNAJC5-26) is a subclass of co-chaperones that has attracted recent attention due to the identification of mutations that are linked with parkinsonism. Here, we focus on DNAJC13, which encodes Receptor-Mediated Endocytosis 8 (RME8), a co-chaperone that facilitates membrane recycling and cargo sorting of endocytosed proteins. RME8 is primarily localized at the early endosome membrane which serves as a switchboard for protein and membrane traffic. In Parkinson’s disease (PD) patients, different mutations of RME8 have been identified, however, more evidence are needed to understand the roles of RME8 in Parkinsonism in vivo. Our proposal will systematically evaluate the 1) behavioral, 2) pathological and 3) cellular changes in novel RME8 mouse models, as a function of age, and determine if they replicate PD features. Our objective is to define the functions of RME8 in Parkinsonism and identify points of therapeutic intervention for PD.