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Papanikolopoulou, K., Kosmidis, S., Grammenoudi, S., Skoulakis, E.M. (2010). Phosphorylation differentiates tau-dependent neuronal toxicity and dysfunction.  Biochem. Soc. Trans. 38(4): 981--987.
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FBrf0211366
Publication Type
Research paper
Abstract

The heterogeneous pathology of tauopathies and the differential susceptibility of different neuronal types to WT (wild-type) and mutant tau suggest that phosphorylation at particular sites rather than hyperphosphorylation mediates toxicity or dysfunction in a cell-type-specific manner. Pan-neuronal accumulation of tau in the Drosophila CNS (central nervous system) specifically affected the MBs (mushroom body neurons), consistent with neuronal type-specific effects. The MB aberrations depended, at least in part, on occupation of two novel phosphorylation sites: Ser(238) and Thr(245). The degree of isoform-specific MB aberrations was paralleled by defects in associative learning, as blocking putative Ser(238) and Thr(245) phosphorylation yielded structurally normal, but profoundly dysfunctional, MBs, as animals accumulating the mutant protein exhibited strongly impaired associative learning. Similarly dysfunctional MBs were obtained by temporally restricting tau accumulation to the adult CNS, which also altered the tau phosphorylation pattern. Our data clearly distinguish tau-dependent neuronal degeneration and dysfunction and suggest that temporal differences in occupation of the same phosphorylation sites are likely to mediate these distinct effects of tau.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Biochem. Soc. Trans.
    Title
    Biochemical Society Transactions
    Publication Year
    1973-
    ISBN/ISSN
    0300-5127
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