Investigating the Functions of RME8 in Parkinson's Disease

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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.