Neuropeptidome and gpcrome of stick insect: Specific structural and functional aspects of allatostatin receptor

Abstract

The arthropods constitute about three-quarters of the world’s animal species. The molecules that regulate many physiological events, from the feeding to develop ment, from locomotion to the social behavior, from the reproductive behavior to the intestinal motility, are the neuropeptides and their cognate receptors. Carausius mo rosus, also known as laboratory rodent, is a species that is studied on locomotion and can easily reproduce via parthenogenesis. On the other hand, among the arthropod neuropeptides, those that regulate Juvenile Hormone, namely allatostatin (AST), is specially important. The subject of this thesis is understanding the interaction be tween allatostatin C receptor (AlstR-C) of C. morosus and AST-C, as well as finding the other neuropeptides and GPCRs. At the beginning of our work, it was found that amino acids were conserved in the ligand binding pocket of AlstR-C and these amino acids were mutated and utilized in atomic force microscopy studies. This IXTPP mo tif, located in the third extracellular loop, together with the N-terminus were found to be important for this interaction. RNA sequencing analysis was then performed to access other AlstR types and AST peptides. As a result,at least 23 different neu ropeptide transcripts and 43 GPCR transcripts were obtained from adult C. morosus. Tissue expression profiles of these GPCRs were found. This information will facilitate future neuropeptide-GPCR studies. In this study, about the Alstr-AST system being homologous to the somatostatin receptor of human, we have also asked whether this neuropeptide may affect the proliferation of cancer cells. However, both XTT and in vivo xenograft experiments showed that the peptide or active receptor does not affect tumor growth.