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DINeR

A Database for Insect Neuropeptide Research

Search the database for information about the various species and neuropeptides of interest

Insect Neuropeptides - Prothoracicotropic hormone

Introduction

Prothoracicotropic hormone (PTTH) was first identified in the silk moth Bombyx mori where it regulates production and release of ecdysone (Ecd) in the prothoracic gland (Kataoka et al., 1991). The Bombyx PTTH is a homodimer of about 25 kDa where each monomer consists of 109 amino acids of which seven are cysteines. Six of these cysteines form three internal disulfide bridges in each monomer, and the seventh forms an intermolecular bridge to the other monomer (Kataoka et al., 1991). PTTH has been identified in several lepidopteran insects, and although the amino acid sequences are variable, the positions of the seven cysteines, and therefore the folding structure of the dimeric peptide, are well conserved (see Rybczynski, 2005; Marchal et al., 2009). The PTTH peptides are additionally characterized by several hydrophobic regions and a glycosylation site (see Marchal et al., 2009). The Drosophila PTTH precursor gene (CG13687), which was identified relatively late, can give rise to a peptide dimer very similar to that in lepidopterans (McBrayer et al., 2007). In Drosophila, the PTTH receptor is encoded on the gene torso (CG1389) and is a receptor tyrosine kinase (Rewitz et al., 2009).

Location

PTTH seem to be exclusively distributed in 2 pairs of large neurosecretory cells in the pars lateralis of the brain in all studied insects (Nagasawa et al., 1986; Sauman and Reppert, 1996; McBrayer et al., 2007; Marchal et al., 2009). These neurons have axon terminations in the prothoracic glands. In Drosophila the torso receptor is expressed in the cells of the prothoracic gland and activation of torso phosphorylates extracellular signal regulated kinase, ERK (Rewitz et al., 2009).

Function

In insects, the timing of molts and metamorphosis is coordinated by the circulating titer of the steroid hormone ecdysone (Gilbert et al., 2002). As the name indicates, PTTH regulates biosynthesis and maybe release of ecdysone in the prothoracic gland during development. In Drosophila, genetic ablation of the PTTH neurons does not affect adult emergence, but delayed development which resulted in bigger larvae, pupae and adults (Rewitz et al., 2009). This indicates that PTTH regulates developmental timing via ecdysone production, but the peptide is not necessary for normal ecdysis. A further layer in the regulation of ecdysone production was discovered recently. The insulin-like peptide 8 (DILP8) released from imaginal discs, and its receptor Lgr3 expressed on brain neurons are part of signal pathway that can regulate ecdysone production upon damage of disc tissues (Colombani et al., 2015; Vallejo et al., 2015). After activation by DILP8, the Lgr3 expressing brain interneurons, signal to the PTTH neurons and thus developmental timing can be correlated with growth of tissues. A recent finding is that cells of the prothoracic gland may release vesicular bound ecdysone in a calcium dependent manner in addition to the previously suggested diffusion through membranes (Yamanaka et al., 2016). Thus, there may be additional signals regulating ecdysone release.

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Suggested Reviews

  • Marchal, E., Vandersmissen, H.P., Badisco, L., Van De Velde, S., Verlinden, H., Iga, M., Van Wielendaele, P., Huybrechts, R., Simonet, G., Smagghe, G., and Vanden Broeck, J. (2010). Control of ecdysteroidogenesis in prothoracic glands of insects: a review. Peptides 31, 506-519.
    View Review
  • Ou, Q., Zeng, J., Yamanaka, N., Brakken-Thal, C., O'connor, M.B., and King-Jones, K. (2016). The Insect Prothoracic Gland as a Model for Steroid Hormone Biosynthesis and Regulation. Cell reports 16, 247-262.
    View Review
  • Rybczynski R. (2005) Prothoracicotropic hormone. In: Gilbert LI, Iatrou K, Gill SS, editors. Comprehensive molecular insect science. Oxford: Elsevier; 2005. p.61–123.
    View Review

References

  • Colombani, J., Andersen, D.S., Boulan, L., Boone, E., Romero, N., Virolle, V., Texada, M., and Leopold, P. (2015). Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability. Current biology : CB 25, 2723-2729.
  • Vallejo, D.M., Juarez-Carreno, S., Bolivar, J., Morante, J., and Dominguez, M. (2015). A brain circuit that synchronizes growth and maturation revealed through Dilp8 binding to Lgr3. Science 350, aac6767.
  • Gilbert, L.I., Rybczynski, R., and Warren, J.T. (2002). Control and biochemical nature of the ecdysteroidogenic pathway. Annual review of entomology 47, 883-916.
  • Marchal, E., Vandersmissen, H.P., Badisco, L., Van De Velde, S., Verlinden, H., Iga, M., Van Wielendaele, P., Huybrechts, R., Simonet, G., Smagghe, G., and Vanden Broeck, J. (2010). Control of ecdysteroidogenesis in prothoracic glands of insects: a review. Peptides 31, 506-519.
  • Kataoka, H., Nagasawa, H., Isogai, A., Ishizaki, H., and Suzuki, A. (1991). Prothoracicotropic hormone of the silkworm, Bombyx mori: amino acid sequence and dimeric structure. Agric Biol Chem 55, 73-86.
  • McBrayer, Z., Ono, H., Shimell, M., Parvy, J.P., Beckstead, R.B., Warren, J.T., Thummel, C.S., Dauphin-Villemant, C., Gilbert, L.I., and O'connor, M.B. (2007). Prothoracicotropic hormone regulates developmental timing and body size in Drosophila. Dev Cell 13, 857-871.
  • Rybczynski R. (2005) Prothoracicotropic hormone. In: Gilbert LI, Iatrou K, Gill SS, editors. Comprehensive molecular insect science. Oxford: Elsevier; 2005. p.61–123.
  • Sauman, I., and Reppert, S.M. (1996). Molecular characterization of prothoracicotropic hormone (PTTH) from the giant silkmoth Antheraea pernyi: developmental appearance of PTTH-expressing cells and relationship to circadian clock cells in central brain. Developmental biology 178, 418-429.
  • Yamanaka, N., Marques, G., and O'connor, M.B. (2015). Vesicle-Mediated Steroid Hormone Secretion in Drosophila melanogaster. Cell 163, 907-919.