A Database for Insect Neuropeptide Research

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

Insect Neuropeptides - GPA2


Insect homologs of the glycoproteins GPA2 and GPB5 were first identified and characterized in Drosophila melanogaster (Hsu et al., 2002; Sudo et al., 2005). These glycoproteins are also found throughout Bilateria (Jékely, 2013). Insect GPA2 and GPB5 each contain 10 highly conserved cysteine residues. These allow for the formation of a cysteine-knot structure which is characteristic of glycoprotein hormones (Paluzzi et al., 2014; Sudo et al., 2005). GPA2 and GPB5 form a heterodimer, which activates a leucine-rich repeat-containing GPCR (LGR); the first insect GPA2/GPB5 receptor was also deorphanized in D. melanogaster (Sudo et al., 2005).


Insect GPA2/GPB5 expression has so far only been localized in D. melanogaster (Sellami et al., 2011). In larvae, GPA2/GPB5 transcripts are expressed in four pairs of bilateral cells in the first four abdominal neuromeres. GPB5-GAL4 driven EGFP localization showed that these cells also persist in the adults. In addition, expression is also observed in a pair of cells in the pars intercerebralis and another pair of cells in the suboesophageal ganglion.


In D. melanogaster, genetic ablation of GPA2/GPB5 cells reduces survival to the adult stage (Sellami et al., 2011). In this study, it was hypothesized that GPA2/GPB5 may function as an anti-diuretic hormone in insects since its receptor is enriched in the hindgut and Malpighian tubules (tissues associated with ion and water homeostasis). In light of this, GPA2/GPB5 has recently been shown to regulate ion transport (specifically Na+ and K+) across A. aegypti hindgut (Paluzzi et al., 2014).

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Suggested Reviews

  • Rocco, D.A., Paluzzi, J.P., 2016. Functional role of the heterodimeric glycoprotein hormone, GPA2/GPB5, and its receptor, LGR1: An invertebrate perspective. Gen Comp Endocrinol pii: S0016, 1–8. doi:10.1016/j.ygcen.2015.12.011
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  • Hsu, S.Y., Nakabayashi, K., Bhalla, A., 2002. Evolution of glycoprotein hormone subunit genes in bilateral metazoa: identification of two novel human glycoprotein hormone subunit family genes, GPA2 and GPB5. Mol. Endocrinol. 16, 1538–51. doi:10.1210/mend.16.7.0871
  • Jékely, G., 2013. Global view of the evolution and diversity of metazoan neuropeptide signaling. Proc. Natl. Acad. Sci. U. S. A. 110, 8702–7. doi:10.1073/pnas.1221833110
  • Paluzzi, J.-P., Vanderveken, M., O’Donnell, M.J., 2014. The heterodimeric glycoprotein hormone, GPA2/GPB5, regulates ion transport across the hindgut of the adult mosquito, Aedes aegypti. PLoS One 9, 1–14. doi:10.1371/journal.pone.0086386
  • Sellami, A., Agricola, H.J., Veenstra, J. a., 2011. Neuroendocrine cells in Drosophila melanogaster producing GPA2/GPB5, a hormone with homology to LH, FSH and TSH. Gen. Comp. Endocrinol. 170, 582–588. doi:10.1016/j.ygcen.2010.11.015
  • Sudo, S., Kuwabara, Y., Park, J. Il, Sheau, Y.H., Hsueh, A.J.W., 2005. Heterodimeric fly glycoprotein hormone-α2 (GPA2) and glycoprotein hormone-β5 (GPB5) activate fly leucine-rich repeat-containing G protein-coupled receptor-1 (DLGR1) and stimulation of human thyrotropin receptors by chimeric fly GPA2 and human GPB5. Endocrinology 146, 3596–3604. doi:10.1210/en.2005-0317