Study of tauopathies by comparing Drosophila and human tau in Drosophila
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The microtubule-binding protein tau has been investigated for its contribution to various neurodegenerative disorders. However, the findings from transgenic studies, using the same tau transgene, vary widely among different laboratories. Here, we have investigated the potential mechanisms underlying tauopathies by comparing Drosophila (d-tau) and human (h-tau) tau in a Drosophila model. Overexpression of a single copy of either tau isoform in the retina results in a similar rough eye phenotype. However, co-expression of Par-1 with d-tau leads to lethality, whereas co-expression of Par-1 with h-tau has little effect on the rough eye phenotype. We have found analogous results by comparing larval proteomes. Through genetic screening and proteomic analysis, we have identified some important potential modifiers and tau-associated proteins. These results suggest that the two tau genes differ significantly. This comparison between species-specific isoforms may help to clarify whether the homologous tau genes are conserved.
KeywordsTau Tauopathy Comparison Conservation Drosophila
We are grateful to Prof. Rongqiao He for his manuscript annotation, to Prof. Kejing Deng (Fudan University, China), Mel B. Feany, Efthimios M.C. Skoulakis, Bingwei Lu, and Suzanne Eaton for kindly donating valuable fly lines, and to Dr. Jianzheng Guo, Shiyu Xu, and Ziyou Cui for their constructive advice regarding our work.
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