title: X11/Mint genes control polarized localization of axonal membrane proteins in vivo.
abstract: Mislocalization of axonal proteins can result in misassembly and/or miswiring of neural circuits, causing disease. To date, only a handful of genes that control polarized localization of axonal membrane proteins have been identified. Here we report that Drosophila X11/Mint proteins are required for targeting several proteins, including human amyloid precursor protein (APP) and Drosophila APP-like protein (APPL), to axonal membranes and for their exclusion from dendrites of the mushroom body in Drosophila, a brain structure involved in learning and memory. Axonal localization of APP is mediated by an endocytic motif, and loss of X11/Mint results in a dramatic increase in cell-surface levels of APPL, especially on dendrites. Mutations in genes required for endocytosis show similar mislocalization of these proteins to dendrites, and strongly enhance defects seen in X11/Mint mutants. These results suggest that X11/Mint-dependent endocytosis in dendrites may serve to promote the axonal localization of membrane proteins. Since X11/Mint binds to APP, and abnormal trafficking of APP contributes to Alzheimer's disease, deregulation of X11/Mint may be important for Alzheimer's disease pathogenesis.
authors: Department of Neurology, University of California, Los Angeles, Los Angeles, California 90095, USA.
authors: Garrett G
authors: GG
authors: Gross
authors: G Mohiddin
authors: GM
authors: Lone
authors: Lok Kwan
authors: LK
authors: Leung
authors: Volker
authors: V
authors: Hartenstein
authors: Ming
authors: M
authors: Guo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D016764:Cell Polarity / Q000235:genetics*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D024521:Mushroom Bodies / Q000254:growth & development / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000648:ultrastructure; D021381:Protein Transport / Q000235:genetics; D034622:RNA Interference / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513072:Apba1 protein, mouse; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D034281:Dynamins
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