A Role for the Ubiquitin-Proteasome System in Activity-Dependent Presynaptic Silencing

Xiaoping Jiang, Patricia E. Litkowski, Amanda A. Taylor, Ying Lin, B. Joy Snider, Krista L. Moulder

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Chronic changes in electrical excitability profoundly affect synaptic transmission throughout the lifetime of a neuron.Wehave previously explored persistent presynaptic silencing, a form of synaptic depression at glutamate synapses produced by ongoing neuronal activity and by strong depolarization. Here we investigate the involvement of the ubiquitin-proteasome system (UPS) in the modulation of presynaptic function. We found that proteasome inhibition prevented the induction of persistent presynaptic silencing. Specifically, application of the proteasome inhibitor MG-132 (carbobenzoxy-L-leucyl-L-leucyl- L-leucinal) prevented decreases in the size of the readily releasable pool of vesicles and in the percentage of active synapses. Presynaptic silencing was accompanied by decreases in levels of the priming proteins Munc13-1 and Rim1. Importantly, overexpression of Rim1αprevented the induction of persistent presynaptic silencing. Furthermore, strong depolarization itself increased proteasome enzymatic activity measured in cell lysates. These results suggest that modulation of the UPS by electrical activity contributes to persistent presynaptic silencing by promoting the degradation of key presynaptic proteins.

Original languageEnglish
Pages (from-to)1798-1809
Number of pages12
JournalJournal of Neuroscience
Volume30
Issue number5
DOIs
StatePublished - Feb 3 2010

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