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Gross, G.G., Lone, G.M., Leung, L.K., Hartenstein, V., Guo, M. (2013). X11/Mint Genes Control Polarized Localization of Axonal Membrane Proteins in Vivo.  J. Neurosci. 33(19): 8575--8586.
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Research paper

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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PMC3865514 (PMC) (EuropePMC)
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    Publication Type
    J. Neurosci.
    Journal of Neuroscience
    Publication Year
    0270-6474 1529-2401
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