Phosphorylation alters tau distribution and elongates life span in drosophila

Po An Yeh, Ching Jin Chang, Pong Hsien Tu, Harry Iain Wilson, Ju Yi Chien, Chiou Yang Tang, Ming-Tsan Su

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The microtubule-associated tau protein has long been considered an axon-specific protein. Although many articles describe the subcellular localization of tau as regulated by post-modification in cultured cells, the intracellular regulation of its distribution in living animals has yet to be elucidated. In the present study, we demonstrate that phosphorylation alters tau polarity in Drosophila melanogaster. Interestingly, it was observed that expression of phosphorylation-incompetent tau impaired neurite growth more severely than either hyperphosphorylated or pseudophosphorylated tau. We also found that inducible expression of hyper- or pseudo-phosphorylated tau in adult flies strikingly prolonged their lifespan. This study offers an alternative tauopathic model by demonstrating that hyperphosphorylated tau has a beneficial effect on the nervous system. This is also corroborated by common effects seen in a variety of organisms in response to various stresses. We hope that this important animal model leads to a paradigm shift in thinking about hyperphosphorylated tau, which plays a protective role in nervous systems rather than the toxic role that many have historically been given to it.

Original languageEnglish
Pages (from-to)543-556
Number of pages14
JournalJournal of Alzheimer's Disease
Volume21
Issue number2
DOIs
Publication statusPublished - 2010 Jan 1

Keywords

  • Alzheimer's disease
  • Drosophila
  • PP2A
  • animal model
  • lifespan
  • neuroprotection
  • protein localization
  • tau phosphorylation
  • tubulin polymerization

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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  • Cite this

    Yeh, P. A., Chang, C. J., Tu, P. H., Wilson, H. I., Chien, J. Y., Tang, C. Y., & Su, M-T. (2010). Phosphorylation alters tau distribution and elongates life span in drosophila. Journal of Alzheimer's Disease, 21(2), 543-556. https://doi.org/10.3233/JAD-2010-091678