期刊
JOURNAL OF NEUROSCIENCE
卷 33, 期 19, 页码 8575-8586出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5749-12.2013
关键词
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资金
- National Institutes of Health [RO1 NS054814, RO1 NS48396]
- Klingenstein Fellowship Awards in the Neurosciences
- Larry P. Hillblom Foundation
- Glenn Family Foundation
- Alfred P. Sloan Foundation
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.
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