Investigating the Role of Neuropeptide Receptors npr-16 and npr-24 in Caenorhabditis elegans

Abstract

The conserved neuropeptide signaling pathway in C. elegans provides a promising opportunity to further advance our knowledge regarding the molecular basis of behaviour and physiology in higher organisms while paving the way for potential development of therapies for various neurodegenerative disorders. In mammals, the peptide hormone family somatostatin comprises a group of various secretory proteins that control neurotransmission, metabolism, and memory by acting on their respective G-Protein Coupled Receptor (GPCR) to inhibit downstream growth-related genes. In C. elegans over 50 GPCRs act as neuropeptide receptors (npr), many of which have mammalian orthologs including npr-16 and npr-24. Thus, characterization of these receptors will allow discovery of analogous somatostatin signaling in C. elegans that can be used for studying the impact of specific neuropeptide and hormonal dysregulation in humans. Through phenotypic and genetic analysis, we aim to examine the role of npr-16 and npr-24 in C. elegans and determine the potential pathways they operate in by establishing an evolutionary link across species. Our work has determined the impact of knock out mutations on key growth phenotypes in of the C. elegans, including longevity and vitellogenesis, as well as their role in metabolism as shown through the distinct increase in fat content. Furthermore, we have observed a potential evolutionary link between C. elegans npr-16 and npr-24 and Drosophila allatostatin-C by examining the impact of the mutation on key enzymes involved in Juvenile hormone biosynthesis. Characterization of npr-16 and npr-24 will provide a unique opportunity to enhance our knowledge about growth and development in C. elegans and aid further somatostatin-related therapeutic studies in this model organism.