Four-way regulation of mosquito yolk protein precursor genes by juvenile hormone-, ecdysone-, nutrient-, and insulin-like peptide signaling pathways

Abstract

Anautogenous mosquito females require a meal of vertebrate blood in order to initiate the production of yolk protein precursors by the fat body. Yolk protein precursor gene expression is tightly repressed in a state-of-arrest before blood meal-related signals activate it and expression levels rise rapidly. The best understood example of yolk protein precursor gene regulation is the vitellogenin-A gene (vg) of the yellow fever mosquito Aedes aegypti. Vg-A is regulated by (1) juvenile hormone signaling, (2) the ecdysone-signaling cascade, (3) the nutrient sensitive target-of-rapamycin signaling pathway, and (4) the insulin-like peptide (ILP) signaling pathway. A plethora of new studies have refined our understanding of the regulation of yolk protein precursor genes since the last review on this topic in 2005 (Attardo et al., 2005). This review summarizes the role of these four signaling pathways in the regulation of vg-A and focuses upon new findings regarding the interplay between them on an organismal level.

Keywords: ecdysone; insulin; juvenile hormone; mosquito; target of rapamycin; vitellogenesis; yolk proteins.

Figure 1

Model of the 4-way regulation of YPP gene expression in Ae. aegypti. The upper part of the scheme depicts a longitudinal section showing the relative position of the different organs involved. Organ and cell size is not up to scale! The lower part shows the different signals involved and their origins. AAs, amino acids; CA, corpora allata; E, ecdysone; ILPs, insulin-like peptides; JH, juvenile hormone; OEH, ovary ecdysteroidogenic hormone; VB, vertebrate blood; YPPs, yolk protein precursors.

Figure 2

Signaling pathways involved in YPP regulation. (A) Juvenile hormone signaling pathway. JH, juvenile hormone; Met, methoprene tolerant. (B) Ecdysone signaling pathway. 20E, 20 hydroxyecdysone; EcR, ecdysone receptor; USP, ultraspiracle. (C) Nutrient signaling pathway. 4E-BP, 4E-binding protein; TSC, tuberous sclerosis complex; RHEB, RAS homologue enriched in brain; S6K, S6 kinase; TOR, target of rapamycin. (D) Insulin-like peptide signaling pathway. AKT, protein kinase B; FOXO, forkhead box protein O; ILP, insulin-like peptide; IRS, insulin receptor substrate; PI3K, phosphati dylinositide 3-kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-triphosphate; PTEN, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. (E) Schematic of the vg-A promoter with transcription factor binding sites.