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J Neurosci. 2019 Sep 5. pii: 0391-19. doi: 10.1523/JNEUROSCI.0391-19.2019. [Epub ahead of print]

Drosophila Tau negatively regulates translation and olfactory Long-Term Memory, but facilitates footshock habituation and cytoskeletal homeostasis.

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Institute for Fundamental Biomedical Research
Institute for Fundamental Biomedical Research.
Institute for Bioinnovation, Biomedical Sciences Research Centre "Alexander Fleming", Vari, 16672, Greece.


Although the involvement of pathological Tau in neurodegenerative dementias is indisputable, its physiological roles have remained elusive in part because its abrogation has been reported without overt phenotypes in mice and Drosophila. This was addressed using the recently described Drosophila tauKO and Mi(Agarwal-Mawal et al.) mutants and focused on molecular and behavioural analyses. Initially we show that dTau loss precipitates dynamic cytoskeletal changes in the adult Drosophila CNS and translation upregulation. Significantly, we demonstrate for the first-time distinct roles for dTau in adult Mushroom Body (MB)-dependent neuroplasticity as its down-regulation within α´β´neurons impairs habituation. In accord with its negative regulation of translation, dTau loss specifically enhances Protein Synthesis Dependent Long-Term Memory (PSD-LTM), but not Anaesthesia-Resistant Memory. In contrast, elevation of the protein in the MBs yielded premature habituation and depressed PSD-LTM. Therefore, Tau loss in Drosophila dynamically alters brain cytoskeletal dynamics and profoundly affects neuronal proteostasis and plasticity.SIGNIFICANCE STATEMENTWe demonstrate that despite modest sequence divergence, the Drosophila Tau is a true vertebrate Tau ortholog as it interacts with the neuronal microtubule and actin cytoskeleton. Novel physiological roles for dTau in regulation of translation, Long-Term Memory and footshock habituation are also revealed. These emerging insights on Tau physiological functions are invaluable for understanding the molecular pathways and processes perturbed in Tauopathies.

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