| First Author | Chen F | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 4 | Pages | 1636-41 |
| PubMed ID | 20080621 | Mgi Jnum | J:156538 |
| Mgi Id | MGI:4420849 | Doi | 10.1073/pnas.0911516107 |
| Citation | Chen F, et al. (2010) Ubiquitin carboxyl-terminal hydrolase L1 is required for maintaining the structure and function of the neuromuscular junction. Proc Natl Acad Sci U S A 107(4):1636-41 |
| abstractText | The enzyme ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is one of the most abundant proteins in the mammalian nervous system. In humans, UCH-L1 is also found in the ubiquitinated inclusion bodies that characterize neurodegenerative diseases in the brain, suggesting its involvement in neurodegeneration. The physiologic role of UCH-L1 in neurons, however, remains to be further elucidated. For example, previous studies have provided evidence both for and against the role of UCH-L1 in synaptic function in the brain. Here, we have characterized a line of knockout mice deficient in the UCH-L1 gene. We found that, in the absence of UCH-L1, synaptic transmission at the neuromuscular junctions (NMJs) is markedly impaired. Both spontaneous and evoked synaptic activity are reduced; paired pulse-facilitation is impaired, and synaptic transmission fails to respond to high-frequency, repetitive stimulation at the NMJs of UCH-L1 knockout mice. Morphologic analyses of the NMJs further revealed profound structural defects-loss of synaptic vesicles and accumulation of tubulovesicular structures at the presynaptic nerve terminals, and denervation of the muscles in UCH-L1 knockout mice. These findings demonstrate that UCH-L1 is required for the maintenance of the structure and function of the NMJ and that the loss of normal UCH-L1 activity may result in neurodegeneration in the peripheral nervous system. |
