Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia

Eunchai Kang, Katherine E. Burdick, Ju Young Kim, Xin Duan, Junjie U. Guo, Kurt A. Sailor, Dhong Eun Jung, Sundar Ganesan, Sungkyung Choi, Dennis Pradhan, Bai Lu, Dimitrios Avramopoulos, Kimberly Christian, Anil K. Malhotra, Hongjun Song, Guo li Ming

Research output: Contribution to journalArticlepeer-review

Abstract

Disrupted-in Schizophrenia 1 (DISC1), a susceptibility gene for major mental disorders, encodes a scaffold protein that has a multifaceted impact on neuronal development. How DISC1 regulates different aspects of neuronal development is not well understood. Here, we show that Fasciculation and Elongation Protein Zeta-1 (FEZ1) interacts with DISC1 to synergistically regulate dendritic growth of newborn neurons in the adult mouse hippocampus, and that this pathway complements a parallel DISC1-NDEL1 interaction that regulates cell positioning and morphogenesis of newborn neurons. Furthermore, genetic association analysis of two independent cohorts of schizophrenia patients and healthy controls reveals an epistatic interaction between FEZ1 and DISC1, but not between FEZ1 and NDEL1, for risk of schizophrenia. Our findings support a model in which DISC1 regulates distinct aspects of neuronal development through its interaction with different intracellular partners and such epistasis may contribute to increased risk for schizophrenia.

Original languageEnglish (US)
Pages (from-to)559-571
Number of pages13
JournalNeuron
Volume72
Issue number4
DOIs
StatePublished - Nov 17 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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