title: Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning.
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.
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea.
authors.forename: Hanwool
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.
authors.forename: Jinhee
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.
authors.forename: Ryunhee
authors.initials: R
authors.lastname: Kim
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 305-701, Korea.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 305-701, Korea.
authors.forename: Yeunkum
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.
authors.forename: Chungwoo
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.
authors.forename: Jongil
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Anatomy and Division of Brain Korea 21. Biomedical Science, College of Medicine, Korea University, Seoul 136-704, Korea.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Division of Brain Korea 21. Biomedical Science, College of Medicine, Korea University, Seoul 136-704, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.|Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 305-701, Korea.
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
mesh_terms: D000818:Animals; D003214:Conditioning, Classical; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005239:Fear; D055786:Gene Knockout Techniques; D051528:Guanylate Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006720:Homozygote; D007858:Learning; D017774:Long-Term Potentiation / Q000235:genetics*; D008565:Membrane Proteins / Q000378:metabolism*; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000235:genetics*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020543:Proteome; D040901:Proteomics / Q000379:methods; D011595:Psychomotor Agitation / Q000235:genetics; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D020543:Proteome; C000610641:Rnf19a protein, mouse; D044767:Ubiquitin-Protein Ligases; D051528:Guanylate Kinases