title: Dysbindin-1, a schizophrenia-related protein, facilitates neurite outgrowth by promoting the transcriptional activity of p53.
abstract: Genetic variations in the DTNBP1 gene (encoding the protein dysbindin-1) have been implicated as risk factors in the pathogenesis of schizophrenia. Previous studies have indicated that dysbindin-1 functions in the regulation of synaptic activity. Recently, dysbindin-1 has also been documented to be involved in neuronal development. In this study, we identified necdin as a binding partner of dysbindin-1 using a yeast two-hybrid screen. Dysbindin-1 recruits necdin to the cytoplasm, thereby attenuating the repressive effects of necdin on p53 transcriptional activity. Knockdown of dysbindin-1, like knockdown of p53, greatly decreases the expressions of the p53 target genes coronin 1b and rab13, which are required for neurite outgrowth. Moreover, overexpression of p53 restores the neurite outgrowth blocked by dysbindin-1 knockdown. In brains of dysbindin-1 null mice (the sandy strain), p21, Coronin 1b and Rab13 levels are reduced. Furthermore, primary cultured cortical neurons from sandy mice display neurite outgrowth defects when compared with those from wild-type mice. Thus, our data provide evidence that dysbindin-1 has an important role in neurite outgrowth through its regulation of p53's transcriptional activity.
authors.affiliation: Laboratory of Molecular Neuropathology, Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences, Anhui, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.forename: E
authors.initials: E
authors.lastname: Fei
authors.forename: C
authors.initials: C
authors.lastname: Fu
authors.forename: H
authors.initials: H
authors.lastname: Ren
authors.forename: G
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000166:cytology; D003593:Cytoplasm / Q000378:metabolism; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D014158:Transcription, Genetic / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C498992:Dtnbp1 protein, mouse; C574928:Dtnbp1 protein, rat; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C069766:necdin; C072061:coronin proteins; C484177:Rab13 protein, mouse; D020691:rab GTP-Binding Proteins