title: Upregulation of Parkin in endophilin mutant mice.
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.
authors.affiliation: 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.
authors.forename: Mian
authors.initials: M
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Ira
authors.initials: I
authors.lastname: Milosevic
authors.affiliation: 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.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giovedi
authors.affiliation: 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.
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
mesh_terms: D000217:Acyltransferases / Q000172:deficiency* / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins; C504641:endophilin A1 protein, mouse; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases; D034281:Dynamins
keywords: Parkinson; Parkinsonism; auxilin; clathrin; dynamin