SCRAPPER-Dependent Ubiquitination of Active Zone Protein RIM1 Regulates Synaptic Vesicle Release
- 1 September 2007
- journal article
- research article
- Published by Elsevier BV in Cell
- Vol. 130 (5), 943-957
- https://doi.org/10.1016/j.cell.2007.06.052
Abstract
Little is known about how synaptic activity is modulated in the central nervous system. We have identified SCRAPPER, a synapse-localized E3 ubiquitin ligase, which regulates neural transmission. SCRAPPER directly binds and ubiquitinates RIM1, a modulator of presynaptic plasticity. In neurons from Scrapper-knockout (SCR-KO) mice, RIM1 had a longer half-life with significant reduction in ubiquitination, indicating that SCRAPPER is the predominant ubiquitin ligase that mediates RIM1 degradation. As anticipated in a RIM1 degradation defect mutant, SCR-KO mice displayed altered electrophysiological synaptic activity, i.e., increased frequency of miniature excitatory postsynaptic currents. This phenotype of SCR-KO mice was phenocopied by RIM1 overexpression and could be rescued by re-expression of SCRAPPER or knockdown of RIM1. The acute effects of proteasome inhibitors, such as upregulation of RIM1 and the release probability, were blocked by the impairment of SCRAPPER. Thus, SCRAPPER has an essential function in regulating proteasome-mediated degradation of RIM1 required for synaptic tuning.This publication has 51 references indexed in Scilit:
- Loss of α-tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic functionProceedings of the National Academy of Sciences of the United States of America, 2007
- The neuronal microRNA systemNature Reviews Neuroscience, 2006
- Hypo-osmotic shock induces nuclear export and proteasome-dependent decrease of UBL5Biochemical and Biophysical Research Communications, 2006
- Proteasome Inhibition Triggers Activity-Dependent Increase in the Size of the Recycling Vesicle Pool in Cultured Hippocampal NeuronsJournal of Neuroscience, 2006
- TTLL7 Is a Mammalian β-Tubulin Polyglutamylase Required for Growth of MAP2-positive NeuritesJournal of Biological Chemistry, 2006
- RIM function in short- and long-term synaptic plasticityBiochemical Society Transactions, 2005
- Ubiquitin and Protein Turnover in Synapse FunctionNeuron, 2005
- An SCF-like ubiquitin ligase complex that controls presynaptic differentiationNature, 2004
- The Nedd4 family of E3 ubiquitin ligases: functional diversity within a common modular architectureOncogene, 2004
- Staring, a Novel E3 Ubiquitin-Protein Ligase That Targets Syntaxin 1 for DegradationJournal of Biological Chemistry, 2002