Autophagy-related gene 7 is downstream of heat shock protein 27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila
| Autor: | Cheng-Wen Huang, Horng-Dar Wang, Ming-Lun Kang, Wan-Hua Li, Guang-Chao Chen, Shih-Fen Chen, Yi-Chun Chen, Pei-Yu Wang, Chao-Yung Wang, Hong-Wen Tang, Chun-Pu Lin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
endocrine system
animal structures Endocrinology Diabetes and Metabolism Clinical Biochemistry HSP27 Heat-Shock Proteins lcsh:Medicine Eye urologic and male genital diseases Autophagy-Related Protein 7 Drosophila Hsp27 RNA interference Heat shock protein medicine Autophagy Animals Drosophila Proteins Pharmacology (medical) Neurodegeneration Molecular Biology Regulation of gene expression Biochemistry medical Gene knockdown biology Lifespan Research Biochemistry (medical) lcsh:R Gene Expression Regulation Developmental Epistasis Genetic General Medicine Cell Biology medicine.disease Cell biology embryonic structures biology.protein RNA Interference Peptides Atg7 Drosophila Protein |
| Zdroj: | Journal of Biomedical Science, Vol 19, Iss 1, p 52 (2012) Journal of Biomedical Science |
| ISSN: | 1423-0127 1021-7770 |
| Popis: | Background Autophagy 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. Methods The 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. Results We 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. Conclusions We propose that Atg7 acts downstream of Hsp27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|