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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.

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References

  • Casanova J, Struhl G (1989) Localized surface activity of torso, a receptor tyrosine kinase, specifies terminal body pattern in Drosophila. Genes Dev 3:2025–2038

    CAS  Article  PubMed  Google Scholar 

  • Chintapalli VR, Wang J, Dow JA (2007) Using FlyAtlas to identify better Drosophila melanogaster models of human disease. Nat Genet 39:715–720

    CAS  Article  PubMed  Google Scholar 

  • Colombani J, Raisin S, Pantalacci S, Radimerski T, Montagne J, Leopold P (2003) A nutrient sensor mechanism controls Drosophila growth. Cell 114:739–749

    CAS  Article  PubMed  Google Scholar 

  • Colombani J, Bianchini L, Layalle S, Pondeville E, Dauphin-Villemant C, Antoniewski C, Carre C, Noselli S, Leopold P (2005) Antagonistic actions of ecdysone and insulins determine final size in Drosophila. Science 310:667–670

    CAS  Article  PubMed  Google Scholar 

  • Delanoue R, Slaidina M, Leopold P (2010) The steroid hormone ecdysone controls systemic growth by repressing dMyc function in Drosophila fat cells. Dev Cell 18:1012–1021

    CAS  Article  PubMed  Google Scholar 

  • Edgar BA (2006) How flies get their size: genetics meets physiology. Nat Rev Genet 7:907–916

    CAS  Article  PubMed  Google Scholar 

  • Hyun S (2013) Body size regulation and insulin-like growth factor signaling. Cell Mol Life Sci 70:2351–2365

    CAS  Article  PubMed  Google Scholar 

  • Hyun S, Lee JH, Jin H, Nam J, Namkoong B, Lee G, Chung J, Kim VN (2009) Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell 139:1096–1108

    CAS  Article  PubMed  Google Scholar 

  • Jin H, Kim VN, Hyun S (2012) Conserved microRNA miR-8 controls body size in response to steroid signaling in Drosophila. Genes Dev 26:1427–1432

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Katz M, Amit I, Yarden Y (2007) Regulation of MAPKs by growth factors and receptor tyrosine kinases. Biochim Biophys Acta 1773:1161–1176

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Li WX (2005) Functions and mechanisms of receptor tyrosine kinase Torso signaling: lessons from Drosophila embryonic terminal development. Dev Dyn 232:656–672

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Lin JL, Gu SH (2007) In vitro and in vivo stimulation of extracellular signal-regulated kinase (ERK) by the prothoracicotropic hormone in prothoracic gland cells and its developmental regulation in the silkworm, Bombyx mori. J Insect Physiol 53:622–631

    CAS  Article  PubMed  Google Scholar 

  • McBrayer Z, Ono H, Shimell M, Parvy JP, Beckstead RB, Warren JT, Thummel CS, Dauphin-Villemant C, Gilbert LI, O’Connor MB (2007) Prothoracicotropic hormone regulates developmental timing and body size in Drosophila. Dev Cell 13:857–871

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Rewitz KF, Larsen MR, Lobner-Olesen A, Rybczynski R, O’Connor MB, Gilbert LI (2009a) A phosphoproteomics approach to elucidate neuropeptide signal transduction controlling insect metamorphosis. Insect Biochem Mol Biol 39:475–483

    CAS  Article  PubMed  Google Scholar 

  • Rewitz KF, Yamanaka N, Gilbert LI, O’Connor MB (2009b) The insect neuropeptide PTTH activates receptor tyrosine kinase torso to initiate metamorphosis. Science 326:1403–1405

    CAS  Article  PubMed  Google Scholar 

  • Rybczynski R, Gilbert LI (2003) Prothoracicotropic hormone stimulated extracellular signal-regulated kinase (ERK) activity: the changing roles of Ca(2+)- and cAMP-dependent mechanisms in the insect prothoracic glands during metamorphosis. Mol Cell Endocrinol 205:159–168

    CAS  Article  PubMed  Google Scholar 

  • Siegmund T, Korge G (2001) Innervation of the ring gland of Drosophila melanogaster. J Comp Neurol 431:481–491

    CAS  Article  PubMed  Google Scholar 

  • Sprenger F, Stevens LM, Nusslein-Volhard C (1989) The Drosophila gene torso encodes a putative receptor tyrosine kinase. Nature 338:478–483

    CAS  Article  PubMed  Google Scholar 

  • Yamanaka N, Romero NM, Martin FA, Rewitz KF, Sun M, O’Connor MB, Leopold P (2013) Neuroendocrine control of Drosophila larval light preference. Science 341:1113–1116

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank the Bloomington Drosophila Stock Center, the Vienna Drosophila RNAi Center and the Kyoto stock center for the fly stocks used in this study. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2014R1A2A1A11052915) and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant Number: HI14C2380).

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Correspondence to Seogang Hyun.

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J. W. Jun, G. Han and H. M. Yun contributed equally to this study.

Communicated by G. Heldmaier.

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Jun, J.W., Han, G., Yun, H.M. et al. Torso, a Drosophila receptor tyrosine kinase, plays a novel role in the larval fat body in regulating insulin signaling and body growth. J Comp Physiol B 186, 701–709 (2016). https://doi.org/10.1007/s00360-016-0992-2

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  • DOI: https://doi.org/10.1007/s00360-016-0992-2

Keywords

  • Torso
  • Fat body
  • Insulin signaling
  • Body size
  • Drosophila