A Database for Insect Neuropeptide Research

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Insect Neuropeptides - Short neuropeptide F


Peptides of short neuropeptide F (sNPF) type were clearly identified with the sequencing of the Drosophila genome and first annotation of its peptidome (Hewes and Taghert, 2001, Vanden Broeck, 2001), and the gene encoding Drosophila sNPF (CG13968) cloned somewhat later (Lee et al., 2004). The Drosophila precursor gene encodes 4 different sNPFs. The sNPFs are characterized by the C-terminal sequence xPxLRLRFamide and range in size between 8 and 19 amino acids (although a 6 amino acid peptide exists in Aedes aegypti). In Drosophila, A. aegypti and Anopheles gambiae the precursor genes also encode sNPF peptides with an RLRWamide C-terminus (see Nässel and Wegener, 2011). The reason for stating that sNPFs were recently identified is that there was some confusion caused by the existence of longer forms designated neuropeptide F (NPF) and shorter forms that obtained various names, including NPF and RYamides (see Hauser et al., 2010; Nässel and Wegener, 2011). Thus, the identification of separate precursor genes of NPF and sNPF, and later RYamides enabled classification of a number of peptides known from biochemical isolation studies. This analysis also revealed that the other FMRF/FLRFamide peptides constitute distinct groups (myosuppressins, sulfakinins and FMRFamides). sNPFs appear to be restricted to arthropods, although their GPCRs are remotely related to Neuropeptide Y type receptors. Actually, it has been inferred that sNPFs are related to prolactin-releasing peptide in mammals (Jeley, 2013). The first GPCR for sNPFs (NPFR76F or sNPFR1; CG7395) was identified in Drosophila (Mertens et al., 2002; Garczynski et al., 2007), and subsequently in the fire ant Solenopsis invicta and the mosquito Anopheles gambiae and in silico in many more insects (See Nässel and Wegener 2011).


Since the sNPFs share the RFamide with several peptides encoded by other genes it was not straightforward to localize their expression. The first specific antisera to detect sNPF expression, combined with in situ hydridization, were applied to Drosophila (Johard et al., 2008; Nässel et al., 2008 ). In this insect, sNPF is expressed in numerous small interneurons in the CNS, chemosensory cells in the antennae as well as a set of large neurosecretory cells in the brain (Nässel et al., 2008). Notably, a large proportion of the intrinsic Kenyon cells of the mushroom bodies express sNPF (Johard et al., 2008) and sNPF plays a role in learning (Knapek et al., 2013). In the Drosophila larva there are in addition a few neurons associated with the proventriculus. In Bombyx mori, sNPF is expressed in neurons of the frontal ganglion and endocrine cells of the corpora cardiaca (Yamanaka et al., 2008).


Correlated with the widespread distribution of sNPF, quite a wide range of functions has been identified in Drosophila and other insects. These include roles in feeding, growth, osmotic and metabolic stress, modulation of complex locomotor behaviour, modulation of olfactory inputs and olfaction guided behaviour, modulation of taste responses and feeding decisions, circadian clock function, olfactory reward learning, control of hormone release, juvenile hormone biosynthesis and immune response (summarized in Nässel and Wegener 2011; Root et al., 2011; Inagaki et al 2014; Dillen et al., 2016; Shen et al., 2016; Kaneko and Hiruma, 2014).

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Suggested Reviews

  • Nässel, D.R., and Wegener, C. (2011). A comparative review of short and long neuropeptide F signalling in invertebrates: Any similarities to vertebrate neuropeptide Y signalling? Peptides 32(6), 1335-1355. doi: 10.1016/j.peptides.2011.03.013.
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  • Clynen, E., Husson, S.J., and Schoofs, L. (2009). Identification of new members of the (short) neuropeptide F family in locusts and Caenorhabditis elegans. Annals of the New York Academy of Sciences 1163, 60-74. doi: 10.1111/j.1749-6632.2008.03624.x.
  • Dillen, S., Chen, Z., and Vanden Broeck, J. (2016). Nutrient-dependent control of short neuropeptide F transcript levels via components of the insulin/IGF signalling pathway in the desert locust, Schistocerca gregaria. Insect biochemistry and molecular biology 68, 64-70. doi: 10.1016/j.ibmb.2015.11.007.
  • Garczynski SF, Brown MR, Crim JW. Structural studies of Drosophila short neuropeptide F: occurrence and receptor binding activity. Peptides 2006;27:575–82.
  • Hauser, F., Neupert, S., Williamson, M., Predel, R., Tanaka, Y., and Grimmelikhuijzen, C.J. (2010). Genomics and peptidomics of neuropeptides and protein hormones present in the parasitic wasp Nasonia vitripennis. Journal of proteome research 9(10), 5296-5310. doi: 10.1021/pr100570j.
  • Inagaki, H.K., Panse, K.M., and Anderson, D.J. (2014). Independent, reciprocal neuromodulatory control of sweet and bitter taste sensitivity during starvation in Drosophila. Neuron 84, 806-820.
  • Jekely, G. (2013). Global view of the evolution and diversity of metazoan neuropeptide signalling. Proceedings of the National Academy of Sciences of the United States of America 110(21), 8702-8707. doi: 10.1073/pnas.1221833110.
  • Johard, H.A., Enell, L.E., Gustafsson, E., Trifilieff, P., Veenstra, J.A., and Nässel, D.R. (2008). Intrinsic neurons of Drosophila mushroom bodies express short neuropeptide F: Relations to extrinsic neurons expressing different neurotransmitters. J Comp Neurol 507(4), 1479-1496. doi: 10.1002/cne.21636.
  • Kaneko, Y., and Hiruma, K. (2014). Short neuropeptide F (sNPF) is a stage-specific suppressor for juvenile hormone biosynthesis by corpora allata, and a critical factor for the initiation of insect metamorphosis. Developmental biology 393(2), 312-319. doi: 10.1016/j.ydbio.2014.07.014.
  • Knapek, S., Kahsai, L., Winther, A.M., Tanimoto, H., and Nässel, D.R. (2013). Short neuropeptide F acts as a functional neuromodulator for olfactory memory in Kenyon cells of Drosophila mushroom bodies. J Neurosci 33(12), 5340-5345. doi: 10.1523/JNEUROSCI.2287-12.2013.
  • Mertens I, Meeusen T, Huybrechts R, De Loof A, Schoofs L. Characterization of the short neuropeptide F receptor from Drosophila melanogaster. Biochem Biophys Res Commun 2002;297:1140–8.
  • Nässel, D.R., Enell, L.E., Santos, J.G., Wegener, C., and Johard, H.A. (2008). A large population of diverse neurons in the Drosophila central nervous system expresses short neuropeptide F, suggesting multiple distributed peptide functions. BMC Neurosci 9, 90. doi: 1471-2202-9-90 [pii]10.1186/1471-2202-9-90.
  • Nässel, D.R., and Wegener, C. (2011). A comparative review of short and long neuropeptide F signalling in invertebrates: Any similarities to vertebrate neuropeptide Y signalling? Peptides 32(6), 1335-1355. doi: 10.1016/j.peptides.2011.03.013.
  • Root, C.M., Ko, K.I., Jafari, A., and Wang, J.W. (2011). Presynaptic facilitation by neuropeptide signalling mediates odor-driven food search. Cell 145, 133-144.
  • Shen, R., Wang, B., Giribaldi, M.G., Ayres, J., Thomas, J.B., and Montminy, M. (2016). Neuronal energy-sensing pathway promotes energy balance by modulating disease tolerance. Proceedings of the National Academy of Sciences of the United States of America 113(23), E3307-3314. doi: 10.1073/pnas.1606106113.
  • Yamanaka, N., Yamamoto, S., Zitnan, D., Watanabe, K., Kawada, T., Satake, H., et al. (2008). Neuropeptide receptor transcriptome reveals unidentified neuroendocrine pathways. PLoS One 3(8), e3048. doi: 10.1371/journal.pone.0003048.