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- Title
Regulation of Synaptic Structure by Ubiquitin C-Terminal Hydrolase L1.
- Authors
Cartier, Anna E.; Djakovic, Stevan N.; Salehi, Afshin; Wilson, Scott M.; Masliah, Eliezer; Patrick, Gentry N.
- Abstract
Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We found that UCH-L1 activity is rapidly upregulated by NMDA receptor activation, which leads to an increase in the levels of free monomericubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomericubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore,there is a concomitant increase in the size of presynaptic and postsynaptic protein clusters. Interestingly,however,ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1-inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner.
- Subjects
SYNAPSES; UBIQUITIN; HYDROLASES; NEURONS; HIPPOCAMPUS (Brain); NEURAL circuitry; NEURAL transmission; NEUROSCIENCES
- Publication
Journal of Neuroscience, 2009, Vol 29, Issue 24, p7857
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1817-09.2009