Phosphorylation alters tau distribution and elongates life span in Drosophila.
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.
Yeh
Po-An
PA
Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan. paulanny@ntnu.edu.tw
Chang
Ching-Jin
CJ
Tu
Pong-Hsien
PH
Wilson
Harry Iain
HI
Chien
Ju-Yi
JY
Tang
Chiou-Yang
CY
Su
Ming-Tsan
MT
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D008136:Longevity / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D016501:Neurites / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D058105:Polymerization; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D014404:Tubulin; D016875:tau Proteins