Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning

Hanwool Park, Jinhee Yang, Ryunhee Kim, Yan Li, Yeunkum Lee, Chungwoo Lee, Jongil Park, Dongmin Lee, Hyun Kim, Eunjoon Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Article number16410
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Nov 10

ASJC Scopus subject areas

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