title: Dysregulated Dscam levels act through Abelson tyrosine kinase to enlarge presynaptic arbors.
abstract: Increased expression of Down Syndrome Cell Adhesion Molecule (Dscam) is implicated in the pathogenesis of brain disorders such as Down syndrome (DS) and fragile X syndrome (FXS). Here, we show that the cellular defects caused by dysregulated Dscam levels can be ameliorated by genetic and pharmacological inhibition of Abelson kinase (Abl) both in Dscam-overexpressing neurons and in a Drosophila model of fragile X syndrome. This study offers Abl as a potential therapeutic target for treating brain disorders associated with dysregulated Dscam expression.
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, United States.
authors.forename: Gabriella R
authors.initials: GR
authors.lastname: Sterne
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, United States.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, United States.
authors.forename: Bing
authors.initials: B
authors.lastname: Ye
mesh_terms: D000818:Animals; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; D011505:Protein-Tyrosine Kinases; C506548:Abl protein, Drosophila
keywords: Abl; D. melanogaster; Dscam; fragile X syndrome; neuronal development; neuroscience; presynaptic terminals; tyrosine kinase inhibitors