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Study of tauopathies by comparing Drosophila and human tau in Drosophila

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Abstract

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.

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Acknowledgements

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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Authors and Affiliations

  1. State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Xinping Chen, Weijie Liu, Huimin Lu & Aike Guo

  2. Graduate School, Chinese Academy of Sciences, Beijing, 100049, China

    Xinping Chen & Weijie Liu

  3. Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Key Laboratory of Neurobiology, Chinese Academy of Sciences, Shanghai, 200031, China

    Junbo Huang, Dawei Cao, Guoying Yang & Aike Guo

  4. Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China

    Yan Li

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  1. Xinping Chen
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Correspondence to Aike Guo.

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This study was supported by the National Science Foundation of China (30270341; 30630028), the Multidisciplinary Program (Brain and Mind) of the Chinese Academy of Sciences, the Major State Basic Research Program (“973 program”; G2000077800; G2006CB806600; 2006CB911003), the Precedent Project of Important Intersectional Disciplines in the Knowledge Innovation Engineering of the Chinese Academy of Sciences (KJCX1-09-03).

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Chen, X., Li, Y., Huang, J. et al. Study of tauopathies by comparing Drosophila and human tau in Drosophila . Cell Tissue Res 329, 169–178 (2007). https://doi.org/10.1007/s00441-007-0401-y

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