Interaction between FEZ1 and DISC1 in Regulation of Neuronal Development and Risk for Schizophrenia

被引：80

作者：

Kang, Eunchai ^{[1
,2
]}

Burdick, Katherine E. ^{[6
,7
,8
]}

Kim, Ju Young ^{[1
,3
]}

Duan, Xin ^{[1
,4
]}

Guo, Junjie U. ^{[1
,4
]}

Sailor, Kurt A. ^{[1
,4
]}

Jung, Dhong-Eun ^{[1
]}

Ganesan, Sundar ^{[9
]}

Choi, Sungkyung ^{[1
]}

Pradhan, Dennis ^{[1
,4
]}

Lu, Bai ^{[9
]}

Avramopoulos, Dimitrios ^{[2
,5
]}

Christian, Kimberly ^{[1
,3
]}

Malhotra, Anil K. ^{[6
,7
,8
]}

Song, Hongjun ^{[1
,2
,3
,4
]}

Ming, Guo-li ^{[1
,3
,4
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA

[6] N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY 11004 USA

[7] Albert Einstein Coll Med, Dept Psychiat, New York, NY 10461 USA

[8] Feinstein Inst Med Res, Manhasset, NY 11004 USA

[9] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA

来源：

NEURON | 2011年 / 72卷 / 04期

关键词：

ADULT NEUROGENESIS; NEURITE OUTGROWTH; STEM-CELL; BRAIN; GENE; PROTEIN; DISRUPTED-IN-SCHIZOPHRENIA-1; ASSOCIATION; BINDING; TRANSLOCATION;

D O I：

10.1016/j.neuron.2011.09.032

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Disrupted-in Schizophrenia 1 (DISCI), 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 DISCI, 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.

引用

页码：559 / 571

页数：13

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