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- Title
Ubiquitin Homeostasis Is Critical for Synaptic Development and Function.
- Authors
Ping-Chung Chen; Bhattacharyya, Bula J.; Hanna, John; Minkel, Heather; Wilson, Julie A.; Finley, Daniel; Miller, Richard J.; Wilson, Scott M.
- Abstract
Theubiquitin-proteasomesystem(UPS)controls proteinabundanceandis essential formanyaspects ofneuronalfunction. In ataxia (axJ) mice, profound neurological and synaptic defects result from a loss-of-function mutation in the proteasome-associated deubiquitinating enzyme Usp14, which is required for recycling ubiquitin from proteasomal substrates. Here, we show that transgenic complementation of axJ mice with neuronally expressed ubiquitin prevents early postnatal lethality, restores muscle mass, and corrects developmental and functional deficits resultingfromthe loss ofUsp14,demonstratingthat ubiquitin deficiency isamajorcauseof the neurological defectsobservedin theaxJ mice.We also show that proteasome components are normally induced during the first 2 weeks of postnatal development, which coincides with dramatic alterations in polyubiquitin chain formation. These data demonstrate a critical role for ubiquitin homeostasis in synaptic development and function, and show that ubiquitin deficiency may contribute to diseases characterized by synaptic dysfunction.
- Subjects
UBIQUITIN; SYNAPSES; HOMEOSTASIS; LABORATORY mice; BRAIN function localization; GENETIC mutation; PROTEASOMES; GENE expression; ATAXIA
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 48, p17505
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2922-11.2011