DISC1- NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1

Atsushi Kamiya, Toshifumi Tomoda, Jennifer Chang, Manabu Takaki, Caixin Zhan, Masahiko Morita, Matthew B. Cascio, Sarah Elashvili, Hiroyuki Koizumi, Yasukazu Takanezawa, Faith Dickerson, Robert Yolken, Hiroyuki Arai, Akira Sawa

Research output: Contribution to journalArticle

131 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3313-3323
Number of pages11
JournalHuman Molecular Genetics
Volume15
Issue number22
DOIs
Publication statusPublished - Nov 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Kamiya, A., Tomoda, T., Chang, J., Takaki, M., Zhan, C., Morita, M., Cascio, M. B., Elashvili, S., Koizumi, H., Takanezawa, Y., Dickerson, F., Yolken, R., Arai, H., & Sawa, A. (2006). DISC1- NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1. Human Molecular Genetics, 15(22), 3313-3323. https://doi.org/10.1093/hmg/ddl407