Neuropeptides are important chemical signals that bind to receptor proteins on their cellular targets. This binding elicits biochemical changes that lead to profound effects on the development and physiology of organisms. The focus of this project is to identify the receptor protein for the insect neuropeptide, allatotropin (AT), by using a combination of molecular biological, biochemical, and bioinformatics approaches. AT has multiple functions which include the regulation of ion transport across the midgut. Ion transport is a fundamental process which is an essential component of every eukaryotic cell, and the identification of the receptor for AT will provide a unique approach to determine the mechanisms by which ion transport is controlled through interfering with its action by using RNA interference technology. This project will provide the experimental tools to clarify the responsiveness of the known target tissues to AT, investigate its interactions with other neuropeptides, and identify novel targets. The results might lead to the development of safe and novel methods to control insect pests by targeting pathways that are specific to AT action. This project includes a significant training component in which a postdoctoral fellow and undergraduate researchers will receive multidisciplinary and integrative training that will encourage the development of independence and problem solving skills that are necessary for a successful career in science.
Neuropeptides are small signalling molecules that are produced by and secreted from specialized cells in both invertebrates and vertebrates. They exert dramatic effects on the development, physiology, and behavior of organisms. We have functionally characterized the receptor for an insect neuropeptide (allatotropin)that exerts several important functions during different stages of the insect's life. Allatotropin is produced with several additional allatotropin-like peptides that share a common biological role. However, the exact nature of the peptides produced changes in a dynamic manner during the insect's life. Our studies have identified a high affinity receptor for these peptides, but also suggest that there might be two different receptors for allatotropin that might have different properties. We have followed up on these observations by synthesizing and testing peptide analogs using two different biological assays. The functional properties of these analogs support the hypothesis that more than one receptor might be involved. During the course of these studies, we have identified a potent peptide antagonist against allatotropin, but not the allatotropin like peptides. This provides a powerful tool to discriminate between the biological functions of allatotropin and allatotropin-like peptides. This is an important step to understanding the complexities that likely exist in all cell signalling systems. This newly-discovered peptide antagonist will serve as a lead compound that may ultimately lead to the development of a biologically rational and environmentally safe pest control strategy based on the defined actions of an insect neuropeptide.
