X11/MintGenes Control Polarized Localization of Axonal Membrane Proteinsin Vivo
| Autor: | L. K. Leung, Volker Hartenstein, Garrett G. Gross, Ming Guo, G. M. Lone |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Dynamins
Green Fluorescent Proteins Endocytic cycle Nerve Tissue Proteins Endocytosis Cell polarity Amyloid precursor protein Animals Drosophila Proteins Mushroom Bodies Adaptor Proteins Signal Transducing Neurons biology General Neuroscience Cell Polarity Gene Expression Regulation Developmental Membrane Proteins Articles Dendrites Axons Transport protein Cell biology Protein Transport Membrane protein Larva Mutation Mushroom bodies biology.protein Drosophila RNA Interference Drosophila Protein |
| Zdroj: | The Journal of Neuroscience. 33:8575-8586 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.5749-12.2013 |
| Popis: | 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 thatDrosophilaX11/Mint proteins are required for targeting several proteins, including human amyloid precursor protein (APP) andDrosophilaAPP-like protein (APPL), to axonal membranes and for their exclusion from dendrites of the mushroom body inDrosophila, a brain structure involved in learning and memory. Axonal localization of APP is mediated by an endocytic motif, and loss ofX11/Mintresults 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 inX11/Mintmutants. 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. |
| Databáze: | OpenAIRE |
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