Abstract
Insulin/IGF-like signalling (IIS) is an evolutionarily conserved pathway that has diverse functions in multi-cellular organisms. Mutations that reduce IIS can have pleiotropic effects on growth, development, metabolic homeostasis, fecundity, stress resistance and lifespan. IIS is also modified by extrinsic factors. For instance, in the fruitfly Drosophila melanogaster, both nutrition and stress can alter the activity of the pathway. Here, we test experimentally the hypothesis that a widespread endosymbiont of arthropods, Wolbachia pipientis, can alter the degree to which mutations in genes encoding IIS components affect IIS and its resultant phenotypes. Wolbachia infection, which is widespread in D. melanogaster in nature and has been estimated to infect 30 per cent of strains in the Bloomington stock centre, can affect broad aspects of insect physiology, particularly traits associated with reproduction. We measured a range of IIS-related phenotypes in flies ubiquitously mutant for IIS in the presence and absence of Wolbachia. We show that removal of Wolbachia further reduces IIS and hence enhances the mutant phenotypes, suggesting that Wolbachia normally acts to increase insulin signalling. This effect of Wolbachia infection on IIS could have an evolutionary explanation, and has some implications for studies of IIS in Drosophila and other organisms that harbour endosymbionts.
Highlights
The insulin/IGF-like signalling (IIS) pathway is ubiquitous in multi-cellular animals and may have been involved in the evolution of multi-cellularity itself (Skorokhod et al 1999)
Mutations that reduce the activity of the IIS signalling cascade have pleiotropic effects on many traits, including growth (Brogiolo et al 2001; Butler & Le Roith 2001; Ikeya et al 2002; Rulifson et al 2002), development (Kimura et al 1997), metabolic homeostasis (Saltiel & Kahn 2001), adult lifespan, resistance to stress (Lithgow et al 1995; Clancy et al 2001; Holzenberger et al 2003) and fecundity (Partridge & Gems 2002; Liang et al 2003; Nelson & Padgett 2003; Tatar et al 2003; Broughton et al 2005; Piper et al 2008) in the nematode worm Caenrhabditis elegans, the fruitfly Drosophila melanogaster and the mouse Mus musculus
This effect of Wolbachia removal to drastically shorten the lifespan of daGAL4/UAS-InRDN females is consistent with an accentuation of the inhibitory effect of InRDN expression, resulting in a reduction in IIS to levels detrimental to survival
Summary
The insulin/IGF-like signalling (IIS) pathway is ubiquitous in multi-cellular animals and may have been involved in the evolution of multi-cellularity itself (Skorokhod et al 1999). Wolbachia infection status had no effect on lifespan (figure 2c; table 2 for statistical analysis; electronic supplementary material, figure 2a –c) This effect of Wolbachia removal to drastically shorten the lifespan of daGAL4/UAS-InRDN females is consistent with an accentuation of the inhibitory effect of InRDN expression, resulting in a reduction in IIS to levels detrimental to survival. Even in the presence of Wolbachia, daGAL/UAS-PTEN flies showed severe IIS-related phenotypes including growth, fecundity, fat and AKT phosphorylation, and they were very short-lived (electronic supplementary material, figures 1– 3) Taken together, these data suggest that the removal of the endosymbiont Wolbachia from daGAL4/InRDN females caused a greater inhibitory effect of InRDN expression on IIS, resulting in enhanced IIS-related phenotypes. The data further suggest that ubiquitous expression of InRDN by daGAL4 may have affected fecundity, growth and fat phenotypes via expression during development and/or in other tissues
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