DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1.
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.
Kamiya
Atsushi
A
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tomoda
Toshifumi
T
Chang
Jennifer
J
Takaki
Manabu
M
Zhan
Caixin
C
Morita
Masahiko
M
Cascio
Matthew B
MB
Elashvili
Sarah
S
Koizumi
Hiroyuki
H
Takanezawa
Yasukazu
Y
Dickerson
Faith
F
Yolken
Robert
R
Arai
Hiroyuki
H
Sawa
Akira
A
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
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D012694:Serine