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- Title
Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning.
- Authors
Park, Hanwool; Yang, Jinhee; Kim, Ryunhee; Li, Yan; Lee, Yeunkum; Lee, Chungwoo; Park, Jongil; Lee, Dongmin; Kim, Hyun; Kim, Eunjoon
- Abstract
Protein ubiquitination has a significant influence on diverse aspects of neuronal development and function. Dorfin, also known as Rnf19a, is a RING finger E3 ubiquitin ligase implicated in amyotrophic lateral sclerosis and Parkinson's disease, but its in vivo functions have not been explored. We report here that Dorfin is a novel binding partner of the excitatory postsynaptic scaffolding protein PSD-95. Dorfin-mutant (Dorfin−/−) mice show reduced adult neurogenesis and enhanced long-term potentiation in the hippocampal dentate gyrus, but normal long-term potentiation in the CA1 region. Behaviorally, Dorfin−/− mice show impaired contextual fear conditioning, but normal levels of cued fear conditioning, fear extinction, spatial learning and memory, object recognition memory, spatial working memory, and pattern separation. Using a proteomic approach, we also identify a number of proteins whose ubiquitination levels are decreased in the Dorfin−/− brain. These results suggest that Dorfin may regulate adult neurogenesis, synaptic plasticity, and contextual fear memory.
- Subjects
DEVELOPMENTAL neurobiology; UBIQUITINATION; LIGASES; GENETICS of amyotrophic lateral sclerosis; OBJECT recognition (Computer vision)
- Publication
Scientific Reports, 2015, p16410
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep16410