SIFamide was first isolated from the fleshfly Sarcophaga bullata (Neobellieria bullata ) as a myostimulatory peptide, using the oviduct of Locusta migratoriaas assay (Janssen et al., 1996). In N. bullata the sequence is AYRKPPFNGSIFamide. The sequence of SIFamides is extremely well conserved among arthropods with the consensus C-terminus X1X2RKPPFNGSIFamide (Verleyen et al., 2009). In the locust Schistocerca gregaria, the SIFamide sequence is somewhat different and the peptide N-terminally extended, AAATFRRPPFNGSIFamide (Gellerer et al., 2015). A single receptor for SIFamide (CG10823) was identified in Drosophila (Jorgensen et al., 2006) and in several other insects (Hauser et al., 2006; Verleyen et al., 2009). SIFamide is evolutionary related to vertebrate Neuropeptide FF and Gonadotropin-inhibitory hormone (GnIH) (Jekely et al., 2013; Mirabeau and Joly, 2013).
The distribution of SIFamide in the CNS of insects also appears well conserved. Two pairs of neurons in the pars intercerebralis (PI) have been detected in all insects studied (see Janssen et al., 1996; Verleyen et al., 2009; Terhzaz et al., 2007; Ons et al., 2010). These neurons have widespread branches throughout the brain that innervate most neuropils, except the mushroom bodies. The same neurons also supply processes throughout the ventral nerve cord. In cockroaches and the locust Schistocerca gregaria, the same types of PI neurons were detected in addition to several groups of smaller neurons (Arendt et al., 2016; Gellerer et al., 2015). In S. gregaria the PI neurons co-localize SIFamide and leucokinin (Gellerer et al., 2015; Ludwig et al., 2001). In insects studied so far, SIFamide seems to be restricted to neurons within the CNS, and, thus, probably the peptide has no hormonal or intestinal functions.
In Drosophila, genetic knockdown of SIFamide or ablation of the neurons producing this peptide generates an interesting phenotype: the male flies become promiscuous and will mate females and males with equal vigour, and females become much more receptive to mating (Terhzaz et al., 2007). Thus, SIFamide neurons with their processes invading most parts of the brain (except mushroom bodies) and the peptide SIFamide are involved in control of sexual behaviour. It was shown that the SIFamide receptor is present on large sets of neurons expressing the transcription factor fruitless known to form networks controlling sexual behaviour (Sellami and Veenstra, 2015). Fruitless (Fru) exists in male and female splice forms and male Fru mutants are sterile and display bisexual behaviour. Thus, in Drosophila, SIFamide acts on large sets of neurons organizing mating behaviour. SIFamide also promotes sleep in Drosophila (Park et al., 2014).
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- Verleyen, P., Huybrechts, J., and Schoofs, L. (2009). SIFamide illustrates the rapid evolution in Arthropod neuropeptide research. General and comparative endocrinology 162(1), 27-35. doi: 10.1016/j.ygcen.2008.10.020.
- Arendt, A., Neupert, S., Schendzielorz, J., Predel, R., and Stengl, M. (2016). The neuropeptide SIFamide in the brain of three cockroach species. The Journal of comparative neurology 524(7), 1337-1360. doi: 10.1002/cne.23910.
Gellerer, A., Franke, A., Neupert, S., Predel, R., Zhou, X., Liu, S., Reiher, W., Wegener, C., and Homberg, U. (2015). Identification and distribution of SIFamide in the nervous system of the desert locust Schistocerca gregaria. The Journal of comparative neurology 523, 108-125.
Hauser, F., Cazzamali, G., Williamson, M., Blenau, W., and Grimmelikhuijzen, C.J. (2006). A review of neurohormone GPCRs present in the fruitfly Drosophila melanogaster and the honey bee Apis mellifera. Progress in neurobiology 80(1), 1-19. doi: 10.1016/j.pneurobio.2006.07.005.
Janssen, I., Schoofs, L., Spittaels, K., Neven, H., Vanden Broeck, J., Devreese, B., et al. (1996). Isolation of NEB-LFamide, a novel myotropic neuropeptide from the grey fleshfly. Molecular and cellular endocrinology 117(2), 157-165.
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.
Jorgensen, L.M., Hauser, F., Cazzamali, G., Williamson, M., and Grimmelikhuijzen, C.J. (2006). Molecular identification of the first SIFamide receptor. Biochemical and Biophysical Research Communications 340(2), 696-701. doi: 10.1016/j.bbrc.2005.12.062.
Ludwig, P., Williams, L., Nässel, D.R., Reichert, H., and Boyan, G. (2001). Primary commissure pioneer neurons in the brain of the grasshopper Schistocerca gregaria: development, ultrastructure, and neuropeptide expression. The Journal of comparative neurology 430, 118-130.
Mirabeau, O., and Joly, J.S. (2013). Molecular evolution of peptidergic signalling systems in bilaterians. Proceedings of the National Academy of Sciences of the United States of America 110(22), E2028-2037. doi: 10.1073/pnas.1219956110.
Ons, S., Sterkel, M., Diambra, L., Urlaub, H., and Rivera-Pomar, R. (2011). Neuropeptide precursor gene discovery in the Chagas disease vector Rhodnius prolixus . Insect molecular biology 20(1), 29-44. doi: 10.1111/j.1365-2583.2010.01050.x.
Park, S., Sonn, J.Y., Oh, Y., Lim, C., and Choe, J. (2014). SIFamide and SIFamide receptor defines a novel neuropeptide signalling to promote sleep in Drosophila. Molecules and cells 37(4), 295-301. doi:10.14348/molcells.2014.2371.
Sellami, A., and Veenstra, J.A. (2015). SIFamide acts on fruitless neurons to modulate sexual behaviour in Drosophila melanogaster. Peptides 74, 50-56. doi: 10.1016/j.peptides.2015.10.003.
Terhzaz, S., Rosay, P., Goodwin, S.F., and Veenstra, J.A. (2007). The neuropeptide SIFamide modulates sexual behaviour in Drosophila. Biochemical and Biophysical Research Communications 352(2), 305-310. doi: 10.1016/j.bbrc.2006.11.030.
Verleyen, P., Huybrechts, J., and Schoofs, L. (2009). SIFamide illustrates the rapid evolution in Arthropod neuropeptide research. General and comparative endocrinology 162(1), 27-35. doi: 10.1016/j.ygcen.2008.10.020.