Differential effects of Usp14 and Uch-L1 on the ubiquitin proteasome system and synaptic activity.
Document Type
Article
Publication Date
2008
Keywords
Gene-Expression-Regulation, Hippocampus, Mice-Inbred-C57BL, Mice-Knockout, Mutation, Neuronal-Plasticity, Phenotype, Proteasome-Endopeptidase-Complex, Synapses, Synaptic-Transmission, Ubiquitin, Ubiquitin-Thiolesterase
First Page
539
Last Page
548
JAX Source
Mol Cell Neurosci 2008 Dec; 39(4):539-48.
Abstract
The ubiquitin proteasome pathway has been implicated in the pathogenesis of many neurodegenerative diseases, and alterations in two different deubiquitinating enzymes, Uch-L1 and Usp14, result in neurological phenotypes in mice. We identified a new mutation in Uch-L1 and compared the roles of Uch-L1 and Usp14 in the ubiquitin proteasome system. Deficiencies in either Uch-L1 or Usp14 result in decreased levels of ubiquitin, suggesting that they both regulate ubiquitin stability in the nervous system. However, the effect of ubiquitin depletion on viability and onset of symptoms is more severe in the Usp14-deficient mice, and changes in hippocampal synaptic transmission were only observed in Usp14-deficient mice. In addition, while Usp14 appears to function at the proteasome, Uch-L1 deficiency resulted in up-regulation of lysosomal components, indicating that Uch-L1 and Usp14 may differentially affect the ubiquitin proteasome system and synaptic activity by regulating different pools of ubiquitin in the cell.
Recommended Citation
Walters BJ,
Campbell SL,
Chen PC,
Taylor AP,
Schroeder DG,
Dobrunz LE,
Artavanis TK,
Ploegh HL,
Wilson JA,
Cox GA,
Wilson SM.
Differential effects of Usp14 and Uch-L1 on the ubiquitin proteasome system and synaptic activity. Mol Cell Neurosci 2008 Dec; 39(4):539-48.