title: DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of Lis1 and DISC1 through control of Ndel1 dual-phosphorylation.
abstract: Cell positioning and neuronal network formation are crucial for proper brain function. Disrupted-in-Schizophrenia 1 (DISC1) is anterogradely transported to the neurite tips, together with Lis1, and functions in neurite extension via suppression of GSK3β activity. Then, transported Lis1 is retrogradely transported and functions in cell migration. Here, we show that DISC1-binding zinc finger protein (DBZ), together with DISC1, regulates mouse cortical cell positioning and neurite development in vivo. DBZ hindered Ndel1 phosphorylation at threonine 219 and serine 251. DBZ depletion or expression of a double-phosphorylated mimetic form of Ndel1 impaired the transport of Lis1 and DISC1 to the neurite tips and hampered microtubule elongation. Moreover, application of DISC1 or a GSK3β inhibitor rescued the impairments caused by DBZ insufficiency or double-phosphorylated Ndel1 expression. We concluded that DBZ controls cell positioning and neurite development by interfering with Ndel1 from disproportionate phosphorylation, which is critical for appropriate anterograde transport of the DISC1-complex.
authors.affiliation: Divisions of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, and.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Divisions of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Research Center for Child Mental Development, University of Fukui, Fukui, 910-1193, Japan, Research and Education Program for Life Science, and Departments of Anatomy and Neuroscience, and.
authors.forename: Tokuichi
authors.initials: T
authors.lastname: Iguchi
authors.affiliation: Departments of Anatomy and Neuroscience, and Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Departments of Anatomy and Neuroscience, and United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, 565-0871, Japan, and.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Matsuzaki
authors.affiliation: Departments of Anatomy and Neuroscience, and.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koyama
authors.affiliation: Departments of Anatomy and Neuroscience, and.
authors.forename: Manabu
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Divisions of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Research and Education Program for Life Science, and.
authors.forename: Munekazu
authors.initials: M
authors.lastname: Komada
authors.affiliation: Divisions of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Research Center for Child Mental Development, University of Fukui, Fukui, 910-1193, Japan, Research and Education Program for Life Science, and.
authors.forename: Min-Jue
authors.initials: MJ
authors.lastname: Xie
authors.affiliation: Divisions of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Yagi
authors.affiliation: Departments of Anatomy and Neuroscience, and.
authors.forename: Shoko
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Research and Education Program for Life Science, and Department of Human and Artificial Intelligent Systems, Faculty of Engineering, University of Fukui, Fukui, 910-8507, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Konishi
authors.affiliation: Divisions of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Research and Education Program for Life Science, and.
authors.forename: Minoru
authors.initials: M
authors.lastname: Omi
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, Osaka City University, Osaka, 558-0022, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yoshimi
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, Osaka City University, Osaka, 558-0022, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Tachibana
authors.affiliation: Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, and.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.affiliation: United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, 565-0871, Japan, and.
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.affiliation: Molecular Neuropsychiatry, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Genetic Disease Research, Osaka City University, Graduate School of Medicine, Osaka, 545-8585, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirotsune
authors.affiliation: Departments of Anatomy and Neuroscience, and United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, 565-0871, Japan, and.
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.affiliation: Divisions of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Research Center for Child Mental Development, University of Fukui, Fukui, 910-1193, Japan, Research and Education Program for Life Science, and Departments of Anatomy and Neuroscience, and United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, 565-0871, Japan, and makosato@anat2.med.osaka-u.ac.jp.
authors.forename: Makoto
authors.identifier: http://orcid.org/0000-0002-6805-8351
authors.initials: M
authors.lastname: Sato
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D011247:Pregnancy; D014162:Transfection
chemical_list: D002352:Carrier Proteins; C498794:Disc1 protein, mouse; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; C486015:Ndel1 protein, mouse; D009419:Nerve Tissue Proteins; C485184:enhanced green fluorescent protein; C017800:zinc-binding protein; D049452:Green Fluorescent Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C513190:Pafah1b1 protein, mouse
keywords: anterograde transport; cortical development; microtubule; migration; neurite extension