Expression and functional characterization of a Drosophila neuropeptide precursor with homology to mammalian preprotachykinin A

Peptides structurally related to mammalian tachykinins have recently been i solated from the brain and intestine of several insect species, where they are believed to function as both neuromodulators and hormones. Further evid ence for the signaling role of insect tachykinin-related peptides was provi ded by the cloning and characterization of cDNAs for two tachykinin recepto rs from Drosophila melanogaster. However, no endogenous ligand has been iso lated for the Drosophila tachykinin receptors to date. Analysis of the Dros ophila genome allowed us to identify a putative tachykinin-related peptide prohormone (prepro-DTK) gene. A 1.5-kilobase pair cDNA amplified from a Dro sophila head cDNA library contained an 870-base pair open reading frame, wh ich encodes five novel Drosophila tachykinin-related peptides (called DTK p eptides) with conserved C-terminal FXGXR-amide motifs common to other insec t tachykinin-related peptides. The tachykinin-related peptide prohormone ge ne (Dtk) is both expressed and post-translationally processed in larval and adult midgut endocrine cells and in the central nervous system, with midgu t expression starting at stage 17 of embryogenesis. The predicted Drosophil a tachykinin peptides have potent stimulatory effects on the contractions o f insect gut. These data provide additional evidence for the conservation o f both the structure and function of the tachykinin peptides in the brain a nd gut during the course of evolution.