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J Neurosci. 2014 Dec 3;34(49):16544-9. doi: 10.1523/JNEUROSCI.1710-14.2014.

Upregulation of Parkin in endophilin mutant mice.

Author information

1
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.
2
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, European Neuroscience Institute (ENI), 37077 Göttingen, Germany, and.
3
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, Department of Experimental Medicine, University of Genoa, 16132 Genoa, Italy.
4
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, pietro.decamilli@yale.edu.

Abstract

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.

KEYWORDS:

Parkinson; Parkinsonism; auxilin; clathrin; dynamin

PMID:
25471590
PMCID:
PMC4252559
DOI:
10.1523/JNEUROSCI.1710-14.2014
[Indexed for MEDLINE]
Free PMC Article

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