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Several proteins encoded by PD genes are implicated in synaptic vesicle traffic. Endophilin, a key factor in the endocytosis of synaptic vesicles, was shown to bind to, and be ubiquitinated by, the PD-linked E3 ubiquitin ligase Parkin. Here we report that Parkin's level is specifically upregulated in brain and fibroblasts of endophilin mutant mice due to increased transcriptional regulation. Studies of transfected HEK293T cells show that Parkin ubiquitinates not only endophilin, but also its major binding partners, dynamin and synaptojanin 1. These results converge with the recently reported functional relationship of endophilin to the PD gene LRRK2 and with the identification of a PD-linked synaptojanin 1 mutation, in providing evidence for a link between PD and endocytosis genes.

Original publication

DOI

10.1523/jneurosci.1710-14.2014

Type

Journal article

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Date

12/2014

Volume

34

Pages

16544 - 16549

Addresses

Department of Cell Biology, Howard Hughes Medical Institute and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06510.

Keywords

Brain, Fibroblasts, Animals, Mice, Knockout, Humans, Mice, Dynamins, Phosphoric Monoester Hydrolases, Ubiquitin-Protein Ligases, Acyltransferases, Adaptor Proteins, Signal Transducing, Nerve Tissue Proteins, Endocytosis, Transcription, Genetic, Up-Regulation, Ubiquitination, HEK293 Cells