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

doi:10.1016/j.neuron.2011.09.032

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

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 language	English (US)
Pages (from-to)	559-571
Number of pages	13
Journal	Neuron
Volume	72
Issue number	4
DOIs	https://doi.org/10.1016/j.neuron.2011.09.032
State	Published - Nov 17 2011

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2011.09.032

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Kang, E., Burdick, K. E., Kim, J. Y., Duan, X., Guo, J. U., Sailor, K. A., Jung, D. E., Ganesan, S., Choi, S., Pradhan, D., Lu, B., Avramopoulos, D., Christian, K., Malhotra, A. K., Song, H., & Ming, G. L. (2011). Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia. Neuron, 72(4), 559-571. https://doi.org/10.1016/j.neuron.2011.09.032

@article{6e0c940d268c41a5b3542f2dedb42a52,

title = "Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia",

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.",

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

note = "Funding Information: We thank D. Weinberg, D. Valle, and members of Ming and Song Laboratories for critical comments, L. Liu, Y. Cai, and H. Qasim for technical support, and A. Sawa and A. Kamiya for anti-NDEL1 antibodies. This work was supported by NIH (NS048271, HD069184), NARSAD, and MSCRF to G.-l.M., by NIH (NS047344, AG024984, MH084018, MH087874), IMHRO and Johns Hopkins BSI to H.S., by MH79800, MH080173 and the Donald and Barbara Zucker Foundation to A.K.M., and by MH077807 to K.E.B., J.Y.K., and K.C. were partially supported by postdoctoral fellowships from MSCRF. ",

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doi = "10.1016/j.neuron.2011.09.032",

language = "English (US)",

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T1 - Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia

AU - Kang, Eunchai

AU - Burdick, Katherine E.

AU - Kim, Ju Young

AU - Duan, Xin

AU - Guo, Junjie U.

AU - Sailor, Kurt A.

AU - Jung, Dhong Eun

AU - Ganesan, Sundar

AU - Choi, Sungkyung

AU - Pradhan, Dennis

AU - Lu, Bai

AU - Avramopoulos, Dimitrios

AU - Christian, Kimberly

AU - Malhotra, Anil K.

AU - Song, Hongjun

AU - Ming, Guo li

N1 - Funding Information: We thank D. Weinberg, D. Valle, and members of Ming and Song Laboratories for critical comments, L. Liu, Y. Cai, and H. Qasim for technical support, and A. Sawa and A. Kamiya for anti-NDEL1 antibodies. This work was supported by NIH (NS048271, HD069184), NARSAD, and MSCRF to G.-l.M., by NIH (NS047344, AG024984, MH084018, MH087874), IMHRO and Johns Hopkins BSI to H.S., by MH79800, MH080173 and the Donald and Barbara Zucker Foundation to A.K.M., and by MH077807 to K.E.B., J.Y.K., and K.C. were partially supported by postdoctoral fellowships from MSCRF.

PY - 2011/11/17

Y1 - 2011/11/17

N2 - 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.

AB - 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.

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JO - Neuron

JF - Neuron

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ER -

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

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