Torso, a Drosophila receptor tyrosine kinase, plays a novel role in the larval fat body in regulating insulin signaling and body growth

Abstract

Torso is a receptor tyrosine kinase whose localized activation at the termini of the Drosophila embryo is mediated by its ligand, Trunk. Recent studies have unveiled a second function of Torso in the larval prothoracic gland (PG) as the receptor for the prothoracicotropic hormone, which triggers pupariation. As such, inhibition of Torso in the PG prolongs the larval growth period, thereby increasing the final pupa size. Here, we report that Torso also acts in the larval fat body, regulating body size in a manner opposite from that of Torso in PG. We confirmed the expression of torso mRNA in the larval fat body and its reduction by RNA interference (RNAi). Fat body-specific knockdown of torso, by either of the two independent RNAi transgenes, significantly decreased the final pupal size. We found that torso knockdown suppresses insulin/target of rapamycin (TOR) signaling in the fat body, as confirmed by repression of Akt and S6K. Notably, the decrease in insulin/TOR signaling and decrease of pupal size induced by the knockdown of torso were rescued by the expression of a constitutively active form of the insulin receptor or by the knockdown of FOXO. Our study revealed a novel role for Torso in the fat body with respect to regulation of insulin/TOR signaling and body size. This finding exemplifies the contrasting effects of the same gene expressed in two different organs on organismal physiology.

Prothoracicotropic hormone modulates environmental adaptive plasticity through the control of developmental timing

“…One of the more unexpected findings of this study is that Drosophila PTTH appears to act autonomously for regulating E biosynthesis within the PG, whereas a previous study demonstrated that PTTH in the hemolymph acts non-autonomously, and in a Torso-dependent manner, to regulate larval light avoidance (Yamanaka et al, 2013b). In addition, a recent study showed that Torso expression in the fat body is required for proper insulin signaling and body size control although the ligand involved was not identified (Jun et al, 2016). Since PTTH reaches the PG through the circulatory system in Lepidoptera, it is unlikely that there is an intrinsic functional need to regulate E biosynthesis through direct innervation of the PG, and indeed we found that overexpression of PTTH in the fat body was able to rescue the developmental delay and body size phenotypes of Ptth null mutants (data not shown).…”

Torso-Like Is a Component of the Hemolymph and Regulates the Insulin Signaling Pathway in Drosophila

“…6B; Geminard et al 2009;Rajan & Perrimon, 2012;Sano et al 2015;Delanoue et al 2016;Koyama & Mirth 2016). Interestingly, a recent study found that knocking down tor specifically in the fat body led to a decreased body size, leading the authors to suggest that Tor acts in the fat body to influence insulin signalling via an unknown mechanism (Jun et al 2016). Given the key role of Tsl in the regulation of Tor activity during early embryogenesis, it is therefore possible that Tsl acts in the Tor pathway in the fat body.…”

“…Given the key role of Tsl in the regulation of Tor activity during early embryogenesis, it is therefore possible that Tsl acts in the Tor pathway in the fat body. However, fat body-specific knockdown of tor does not result in a developmental delay (Jun et al 2016), thus this would seem unlikely to be the only role for Tsl in regulating growth and developmental transitions. In addition, experiments that we have performed to detect Tsl or knockdown its expression in the fat body have not provided any evidence of Tsl expression or function in this tissue.…”

Torso-like is a component of the hemolymph and regulates the insulin signalling pathway in Drosophila

“…6B; Geminard et al 2009;Rajan & Perrimon, 2012;Sano et al 2015;Delanoue et al 2016;Koyama & Mirth 2016). Interestingly, a recent study found that knocking down tor specifically in the fat body led to a decreased body size, leading the authors to suggest that Tor acts in the fat body to influence insulin signalling via an unknown mechanism (Jun et al 2016). Given the key role of Tsl in the regulation of Tor activity during early embryogenesis, it is therefore possible that Tsl acts in the Tor pathway in the fat body.…”