title: Disrupted-in-schizophrenia 1 (DISC1) regulates dysbindin function by enhancing its stability.
abstract: Dysbindin and DISC1 are schizophrenia susceptibility factors playing roles in neuronal development. Here we show that the physical interaction between dysbindin and DISC1 is critical for the stability of dysbindin and for the process of neurite outgrowth. We found that DISC1 forms a complex with dysbindin and increases its stability in association with a reduction in ubiquitylation. Furthermore, knockdown of DISC1 or expression of a deletion mutant, DISC1 lacking amino acid residues 403-504 of DISC1 (DISC1(Δ403-504)), effectively decreased levels of endogenous dysbindin. Finally, the neurite outgrowth defect induced by knockdown of DISC1 was partially reversed by coexpression of dysbindin. Taken together, these results indicate that dysbindin and DISC1 form a physiologically functional complex that is essential for normal neurite outgrowth.
authors: From the Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Seol-Ae
authors: SA
authors: Lee
authors: From the Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Seong-Mo
authors: SM
authors: Kim
authors: From the Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Bo Kyoung
authors: BK
authors: Suh
authors: From the Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Hwa-Young
authors: HY
authors: Sun
authors: From the Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Young-Un
authors: YU
authors: Park
authors: From the Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Ji-Ho
authors: JH
authors: Hong
authors: From the Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Cana
authors: C
authors: Park
authors: the Hotchkiss Brain Institute, Departments of Clinical Neurosciences, Cell Biology and Anatomy, and Biochemistry and Molecular Biology, University of Calgary, Calgary T2N 4N1, Canada, and.
authors: Minh Dang
authors: MD
authors: Nguyen
authors: the Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kamiya, Kasugai 480-0392, Japan.
authors: Koh-Ichi
authors: K
authors: Nagata
authors: From the Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors: Joo-Yeon
authors: JY
authors: Yoo
authors: From the Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea, skpark@postech.ac.kr.
authors: Sang Ki
authors: SK
authors: Park
mesh_terms: D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002522:Chlorocebus aethiops; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D025801:Ubiquitin
chemical_list: C412476:DISC1 protein, human; C432416:DTNBP1 protein, human; C498794:Disc1 protein, mouse; C498992:Dtnbp1 protein, mouse; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D009419:Nerve Tissue Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: DISC1; Dysbindin; Neurite Outgrowth; Protein Complex; Protein Stability; Schizophrenia; Ubiquitylation (Ubiquitination)
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