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.
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Eunchai
authors.initials: E
authors.lastname: Kang
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Burdick
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.forename: Junjie U
authors.initials: JU
authors.lastname: Guo
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Sailor
authors.forename: Dhong-Eun
authors.initials: DE
authors.lastname: Jung
authors.forename: Sundar
authors.initials: S
authors.lastname: Ganesan
authors.forename: Sungkyung
authors.initials: S
authors.lastname: Choi
authors.forename: Dennis
authors.initials: D
authors.lastname: Pradhan
authors.forename: Bai
authors.initials: B
authors.lastname: Lu
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Avramopoulos
authors.forename: Kimberly
authors.initials: K
authors.lastname: Christian
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.forename: Guo-li
authors.initials: GL
authors.lastname: Ming
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D055785:Gene Knockdown Techniques; D056726:Genetic Association Studies; D006624:Hippocampus / Q000254:growth & development; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C412476:DISC1 protein, human; C528597:FEZ1 protein, human; D009419:Nerve Tissue Proteins
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