Ubiquitin carboxyl-terminal hydrolase L1 is required for maintaining the structure and function of the neuromuscular junction

Fujun Chen, Yoshie Sugiura, Kalisa Galina Myers, Yun Liu, Weichun Lin

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

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 themuscles in UCH-L1 knockoutmice. 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.

Original languageEnglish (US)
Pages (from-to)1636-1641
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number4
DOIs
StatePublished - Jan 26 2010

Keywords

  • Electrophysiology
  • Knockout mice
  • Neurodegeneration
  • Synaptic transmission

ASJC Scopus subject areas

  • General

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