Ovary ecdysteroidogenic hormone requires a receptor tyrosine kinase to activate egg formation in the mosquito Aedes aegypti

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 112; no. 16; pp. 5057 - 5062
• Main Authors: Vogel, Kevin J, Brown, Mark R, Strand, Michael R
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 21.04.2015; National Acad Sciences
• Subjects: Aedes - enzymology; Aedes aegypti; Animals; Biological Sciences; Cells; Drosophila; Drosophila melanogaster - cytology; Ecdysteroids - metabolism; Female; Gene Knockdown Techniques; Hormones; Insect Proteins - chemistry; Insect Proteins - metabolism; Insulin - metabolism; Mosquitoes; Oogenesis; Ovary - cytology; Ovary - enzymology; Peptides; Phosphorylation; Phylogenetics; Phylogeny; Protein Binding; Protein Multimerization; Protein Structure, Tertiary; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Receptor Protein-Tyrosine Kinases - chemistry; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Steroid - metabolism; RNA Interference; insect; vector; mosquito; oogenesis; reproduction
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1501814112

Mosquitoes are major disease vectors because most species must feed on blood from a vertebrate host to produce eggs. Blood feeding by the vector mosquito Aedes aegypti triggers the release of two neurohormones, ovary ecdysteroidogenic hormone (OEH) and insulin-like peptides (ILPs), which activate multiple processes required for egg formation. ILPs function by binding to the insulin receptor, which activates downstream components in the canonical insulin signaling pathway. OEH in contrast belongs to a neuropeptide family called neuroparsins, whose receptor is unknown. Here we demonstrate that a previously orphanized receptor tyrosine kinase (RTK) from A. aegypti encoded by the gene A AEL001915 is an OEH receptor. Phylogenetic studies indicated that the protein encoded by this gene, designated AAEL001915, belongs to a clade of RTKs related to the insulin receptor, which are distinguished by an extracellular Venus flytrap module. Knockdown of AAEL001915 by RNAi disabled OEH-mediated egg formation in A. aegypti . AAEL001915 was primarily detected in the mosquito ovary in association with follicular epithelial cells. Both monomeric and dimeric AAEL001915 were detected in mosquito ovaries and transfected Drosophila S2 cells. Functional assays further indicated that OEH bound to dimeric AAEL001915, which resulted in downstream phosphorylation of Ak strain transforming factor (Akt). We hypothesize that orthologs of AAEL001915 in other insects are neuroparsin receptors. Significance Mosquitoes are important because several species transmit pathogens that cause major diseases of humans and other vertebrates. Mosquitoes acquire and transmit pathogens because most species must consume blood from a vertebrate host to produce eggs. Thus, a promising strategy for disease control is to interfere with mosquito reproduction. Blood feeding triggers the release of ovary ecdysteroidogenic hormone (OEH) from the mosquito brain, which is a key regulator of egg formation. To function, however, OEH must bind a receptor, which was previously unknown. Here we identify an OEH receptor and show that it is required for egg formation. Targeting OEH–receptor interactions provides opportunities for reducing mosquito reproduction and disease transmission.