title: Dscam expression levels determine presynaptic arbor sizes in Drosophila sensory neurons.
abstract: Expression of the Down syndrome cell-adhesion molecule (Dscam) is increased in the brains of patients with several neurological disorders. Although Dscam is critically involved in many aspects of neuronal development, little is known about either the mechanism that regulates its expression or the functional consequences of dysregulated Dscam expression. Here, we show that Dscam expression levels serve as an instructive code for the size control of presynaptic arbor. Two convergent pathways, involving dual leucine zipper kinase (DLK) and fragile X mental retardation protein (FMRP), control Dscam expression through protein translation. Defects in this regulation of Dscam translation lead to exuberant presynaptic arbor growth in Drosophila somatosensory neurons. Our findings uncover a function of Dscam in presynaptic size control and provide insights into how dysregulated Dscam may contribute to the pathogenesis of neurological disorders.
authors.affiliation: Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Rosemary
authors.initials: R
authors.lastname: Coolon
authors.forename: Bing
authors.initials: B
authors.lastname: Ye
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D007839:Functional Laterality; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D017729:Presynaptic Terminals / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology*; D015398:Signal Transduction / Q000235:genetics; D018709:Statistics, Nonparametric; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D049452:Green Fluorescent Proteins; D020930:MAP Kinase Kinase Kinases; D012333:RNA, Messenger; C491736:Dscam1 protein, Drosophila; C090757:mitogen-activated protein kinase kinase kinase 12