Functional Elucidation of The Adipokinetic Hormone/Corazonin Related Peptide and Insights into Its Receptor Specificity Using Receptor Chimera in Aedes Aegypti Mosquito

Mosquitoes Aedes aegypti are an essential organism to study as they are significant vectors responsible for transmitting arboviral diseases such as Yellow fever, Dengue and Zika virus. The adipokinetic hormone/corazonin-related peptide (ACP) is an insect neuropeptide that is structurally intermediate between corazonin (CRZ) and adipokinetic hormone (AKH). A well-known function of the AKH signaling system is the mobilization of energy while CRZ was initially described as a cardioacceleratory factor. Contrastingly, the role of ACP and its receptor (ACPr) remains unclear in many insects. Despite the structural similarity and the close evolutionary relationship between ACP and AKH, their signaling systems function independently due to the high selectivity of their corresponding receptors. In light of this knowledge, this thesis sought to advance our understanding of the role of the ACP in A. aegypti by mapping the distribution of ACP in the nervous system, examining the ACPr transcript expression in the abdominal ganglia, assessing the possible involvement of ACP in controlling energy substrate levels, and determining adult survival rate after injection with ACP. Moreover, this study aimed to determine the most critical regions of the ACPr necessary for ligand-binding specificity and discern specific residues critical for functional ligand-binding by singly replacing the three ACPr extracellular loops or critical highly conserved residues and incorporating those from the AKH receptor and testing these ACPr chimeras using a heterologous functional assay. Together, this study gives insight to advance our mechanistic understanding of the broad and critical functions of the ACP signaling system in A. aegypti.