Autophagy-related gene 7 is downstream of heat shock protein 27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila

Journal of Biomedical Science

Research

Chun-Pu Lin¹  Guang-Chao Chen²  Hong-Wen Tang²  Ming-Lun Kang³  Yi-Chun Chen³  Shih-Fen Chen³  Wan-Hua Li³  Horng-Dar Wang⁴  Cheng-Wen Huang⁵  Pei-Yu Wang⁶  Chao-Yung Wang⁷ 

[1] Department of Life Science, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, 30013, HsinChu, Taiwan;Institute of Biological Chemistry, 128, Section 2, Academia Road, 115, Nankang, Taipei, Taiwan;Institute of Biotechnology, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, 30013, HsinChu, Taiwan;Institute of Biotechnology, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, 30013, HsinChu, Taiwan;Department of Life Science, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, 30013, HsinChu, Taiwan;Institute of Biotechnology, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, 30013, HsinChu, Taiwan;Institute of Neuroscience, National Chengchi University, 64, Section 2, Zhi-Nan Road, 11605, Taipei, Taiwan;Institute of Neuroscience, National Chengchi University, 64, Section 2, Zhi-Nan Road, 11605, Taipei, Taiwan;Second Section of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan;

关键词: Atg7;    Hsp27;    Neurodegeneration;    Lifespan;    Drosophila;   

DOI  :  10.1186/1423-0127-19-52

 received in 2012-02-02, accepted in 2012-05-23,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundAutophagy and molecular chaperones both regulate protein homeostasis and maintain important physiological functions. Atg7 (autophagy-related gene 7) and Hsp27 (heat shock protein 27) are involved in the regulation of neurodegeneration and aging. However, the genetic connection between Atg7 and Hsp27 is not known.MethodsThe appearances of the fly eyes from the different genetic interactions with or without polyglutamine toxicity were examined by light microscopy and scanning electronic microscopy. Immunofluorescence was used to check the effect of Atg7 and Hsp27 knockdown on the formation of autophagosomes. The lifespan of altered expression of Hsp27 or Atg7 and that of the combination of the two different gene expression were measured.ResultsWe used the Drosophila eye as a model system to examine the epistatic relationship between Hsp27 and Atg7. We found that both genes are involved in normal eye development, and that overexpression of Atg7 could eliminate the need for Hsp27 but Hsp27 could not rescue Atg7 deficient phenotypes. Using a polyglutamine toxicity assay (41Q) to model neurodegeneration, we showed that both Atg7 and Hsp27 can suppress weak, toxic effect by 41Q, and that overexpression of Atg7 improves the worsened mosaic eyes by the knockdown of Hsp27 under 41Q. We also showed that overexpression of Atg7 extends lifespan and the knockdown of Atg7 or Hsp27 by RNAi reduces lifespan. RNAi-knockdown of Atg7 expression can block the extended lifespan phenotype by Hsp27 overexpression, and overexpression of Atg7 can extend lifespan even under Hsp27 knockdown by RNAi.ConclusionsWe propose that Atg7 acts downstream of Hsp27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila.

【 授权许可】

CC BY   
© Chen et al.; licensee BioMed Central Ltd. 2012