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Title: EXPRESSION AND FUNCTIONAL CHARACTERIZATION OF A DROSOPHILA NEUROPEPTIDE PRECURSOR WITH HOMOLOGY TO MAMMALIAN PREPROTACHYKININ A

Author
item SIVITER, RICHARD - UNIVERSITY OF LEEDS
item COAST, GEOFFREY - BIRKBECK COLLEGE
item WINTHER, ASA - STOCKHOLM UNIVERSITY
item Nachman, Ronald
item TAYLOR, CHRISTINE - UNIVERSIT OF LANCASTER
item SHIRRAS, ALAN - UNIVERSITY OF LANCASTER
item COATEST, DAVID - UNIVERSIT OF LEEDS
item ISAAC, R - UNIVERSITY OF LEEDS
item NASSEL, DICK - STOCKHOLM UNIVERSITY

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/8/2000
Publication Date: N/A
Citation: N/A

Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling such pests. The basic premise of this research is that peptides (short chains of amino acids) serve as potent internal messengers in insects to regulate vital functions. Peptides themselves are eunsuitable for control measures due to their instability to enzymes in the circulatory and digestive systems of the insect. New, selective control measures may be developed by designing metabolically stable mimics of these neuropeptides that actively inhibit or over-stimulate functions regulated by them, resulting in disruption of the internal environment of the insect. In this paper, we describe the identification of a precursor (prohormone) to a neuropeptide which regulates aspects of digestion and energy utilization in insects. The work further identifies the organs within the insect that produce this precursor and therefore the hormone itself. Information about the processing and function of critical neuropeptides will aid in the development of strategies to disrupt the processes they regulate within pest insects. This work leads us one step closer to the development of practical neuropeptide-like chemicals that will be effective in controlling certain pest insects in an environmentally friendly fashion.

Technical Abstract: Peptides structurally related to mammalian tachykinins have recently been isolated from brain and intestine of several insect species, where they are believed to function as both neuromodulators and hormones. Further evidence for the signalling role of insect tachykinin-related peptides was provided by the cloning and characterisation of cDNAs for two tachykinin receptors from Drosophila melanogaster. However, no endogenous ligand has been isolated for the Drosophila tachykinin receptors to date. Analysis of the Drosophila genome allowed us to identify a putative tachykinin-related peptide prohormone (preproDTK) gene. A l.5kb cDNA amplified from a Drosophila head cDNA library contained an 870bp open reading frame, which encodes five novel Drosophila tachykinin-related peptides (Dtk) with conserved C-terminal FXGXRamide motifs common to other insect tachykinin related peptides. The tachykinin-related peptide prohormone gene (Dtk) is both expressed and post-translationally processed in larval and adult midgut endocrine cells and in the central nervous system, with midgut expression starting at stage 17 of embryogenesis. The predicted Drosophila tachykinin peptides have potent stimulatory effects on the contractions of insect gut. These data provide additional evidence for the conservation of both the structure and function of the tachykinin peptides in the brain and gut during the course of evolution.