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

Abstract

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.

Developmentally regulated autophagy is required for eye formation in Drosophila

“…In the literature several studies have reported no influence of autophagy on this developmental paradigm [48][49][50][51][52]. Contrary to these data, we found that mutational inactivation of Atg17 and Atg1 can impede eye formation (Fig.…”

“…Previous studies have detected no obvious defect in adult eye morphology when Atg genes are silenced by GMR-Gal4 driver [48,50]. It is possible that GMR-Gal4 is expressed in less excessive levels in the eye disc than ey-Gal4(II) and ey-Gal4(III) do.…”

“…In previous studies, GMR-Gal4 was used to control the expression of UAS-Atg RNAi constructs in the eye disc [48,50]. However, the activity of this driver was only detectable behind the MF (i.e.…”

Autophagy is essential for cardiac morphogenesis during vertebrate development

“…For example, abnormalities in larval development, synapse formation, and eye development are observed in autophagy gene mutant Drosophila. [8][9][10][11][12] In C. elegans, autophagy genes play a role in apoptotic corpse clearance in embryonic development, 13 the L1 larval stage, 14 and the adult gonad, 15 in degrading germline P granules in somatic cells, 16 and in the selective elimination of paternal mitochondria. 17,18 In mice, autophagy genes play an essential role in preimplantation development, survival during the neonatal starvation period, and in the differentiation of several specific cell lineages, including adipocytes, erythrocytes, and lymphocytes (T cells and B-1a cells) (reviewed in ref.…”

Response of heat shock protein genes of the oriental fruit moth under diapause and thermal stress reveals multiple patterns dependent on the nature of stress exposure

“…For example, Hsc70 and Hsp90 interact with ecdysone receptor activation which is vital in ecdysone response pathway (Arbeitman and Hogness 2000), while Hsp27 is known to involve in eye development (Chen et al 2012). Hsp70 and Hsp90 as well as small heat shock proteins (Hsp22, Hsp67Ba, and Hsp67Bc) are also implicated in the maintenance of phenotypic stability under variable environmental conditions (Morrow and Tanguay 2015;Takahashi et al 2010).…”