Upregulation of Parkin in endophilin mutant mice

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Adaptor Proteins, Signal Transducing
  • Nerve Tissue Proteins
  • endophilin A1 protein, mouse
  • Acyltransferases
  • 2-acylglycerophosphate acyltransferase
  • Ubiquitin-Protein Ligases
  • parkin protein
  • synaptojanin
  • Phosphoric Monoester Hydrolases
  • Dynamins