title: DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1.
abstract: Disrupted-In-Schizophrenia-1 (DISC1) is a unique susceptibility gene for major mental conditions, because of the segregation of its genetic variant with hereditary psychosis in a Scottish pedigree. Genetic association studies reproducibly suggest involvement of DISC1 in both schizophrenia and bipolar disorder in several ethnic groups. The DISC1 protein is multifunctional, and a pool of DISC1 in the dynein motor complex is required for neurite outgrowth in PC12 cells as well as proper neuronal migration and dendritic arborization in the developing cerebral cortex in vivo. Here, we show that a specific interaction between DISC1 and nuclear distribution element-like (NDEL1/NUDEL) is required for neurite outgrowth in differentiating PC12 cells. Among several components of the dynein motor complex, DISC1 and NDEL1 are selectively upregulated during neurite outgrowth upon differentiation in PC12 cells. The NDEL1 binding site of DISC1 was narrowed down to a small portion of exon 13, corresponding to amino acids 802-835 of DISC1. We demonstrate that genetic variants of DISC1, proximal to the NDEL1 binding site, affect the interaction between DISC1 and NDEL1.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kamiya
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tomoda
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chang
authors.forename: Manabu
authors.initials: M
authors.lastname: Takaki
authors.forename: Caixin
authors.initials: C
authors.lastname: Zhan
authors.forename: Masahiko
authors.initials: M
authors.lastname: Morita
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Cascio
authors.forename: Sarah
authors.initials: S
authors.lastname: Elashvili
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koizumi
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Takanezawa
authors.forename: Faith
authors.initials: F
authors.lastname: Dickerson
authors.forename: Robert
authors.initials: R
authors.lastname: Yolken
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D012326:RNA Splicing / Q000235:genetics; D051381:Rats; D012694:Serine / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D012694:Serine