title: Interaction between DISC1 and CHL1 in regulation of neurite outgrowth.
abstract: Disrupted-in-schizophrenia 1 (DISC1), a gene susceptible for major mental illnesses, including schizophrenia, plays multiple roles in neural development, including neuronal proliferation, maturation, migration and neurite outgrowth. DISC1 regulates neurite length via interaction with several intracellular proteins, such as NDEL1, FEZ1 and dysbindin. However, the signal transduction mechanism upstream of DISC1 in regulating neurite outgrowth remains to be elucidated. Here we show that DISC1 interacts with the intracellular domain of close homolog of L1 (CHL1), a member of the L1 family of neural cell adhesion molecules. DISC1 and CHL1 proteins co-localize in growth cones of cortical neurons. Moreover, in neurite outgrowth assay, CHL1 rescues the inhibitory effect of DISC1 on the initial phase of neurite outgrowth. Considering the fact that CHL1 also plays crucial roles in neural development, and its coding gene is associated with schizophrenia, our findings indicate that DISC1 and CHL1 may engage in physical and functional interaction in neural development, supporting the notion that DISC1 regulates neurite outgrowth with a receptor belonging to the neural cell adhesion molecules, and disruption of such interaction may contribute to increased risk for schizophrenia.
authors.affiliation: Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Institute for Brain Disorders, Center of Schizophrenia, Capital Medical University, Beijing 100069, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Institute for Brain Disorders, Center of Schizophrenia, Capital Medical University, Beijing 100069, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Institute for Brain Disorders, Center of Schizophrenia, Capital Medical University, Beijing 100069, China. Electronic address: xuyl@ccmu.edu.cn.
authors.forename: Yiliang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Beijing Institute for Brain Disorders, Center of Schizophrenia, Capital Medical University, Beijing 100069, China. Electronic address: yehh@ccmu.edu.cn.
authors.forename: Haihong
authors.initials: H
authors.lastname: Ye
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D000071446:Neuronal Outgrowth; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015815:Cell Adhesion Molecules; C490649:Chl1 protein, mouse; C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins
keywords: CHL1; DISC1; Neural development; Schizophrenia