| First Author | Cartier AE | Year | 2009 |
| Journal | J Neurosci | Volume | 29 |
| Issue | 24 | Pages | 7857-68 |
| PubMed ID | 19535597 | Mgi Jnum | J:155638 |
| Mgi Id | MGI:4414906 | Doi | 10.1523/JNEUROSCI.1817-09.2009 |
| Citation | Cartier AE, et al. (2009) Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1. J Neurosci 29(24):7857-68 |
| abstractText | 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 monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin 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. |
