Nutritional and hormonal regulation of the TOR effector 4E-binding protein (4E-BP) in the mosquito Aedes aegypti.

Autor(es): Roy Saurabh G; Raikhel Alexander S

Resumo: Mosquitoes require blood for egg development, and, as a consequence, they transmit pathogens of devastating diseases. Target of rapamycin (TOR) signaling is a key pathway linking blood feeding and egg development in the mosquito Aedes aegypti. We show that the regulation of the TOR effector translational repressor 4E-BP is finely tuned to the nutritional requirements of the female mosquito, and it occurs at transcriptional and post-translational levels. Immediately after blood feeding, 4E-BP became hyperphosphorylated, suggesting rapid inhibition of its translational repression function. 4E-BP was highly phosphorylated after in vitro incubation of the fat body in the presence of amino acids; this phosphorylation was rapamycin insensitive, in contrast to another TOR target, S6K, phosphorylation of which was rapamycin sensitive. A high level of 4E-BP phosphorylation was also elicited by insulin. Rapamycin and the PI3K inhibitor LY294002 blocked insulin-mediated 4E-BP phosphorylation. RNA-interference depletion of the insulin receptor or Akt resulted in severe reduction of 4E-BP phosphorylation. Phosphorylation and stability of 4E-BP was dependent on its partner eIF4E translation initiation factor. Silencing of 4E-BP resulted in reduction of the life span of adult female mosquitoes. This study demonstrates a dual nutritional and hormonal control of 4E-BP and its role in mosquito egg development.

Palavras-Chave: Amino acids; Insulin; Translation; Blood-feeding insect

Imprenta: FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, v. 26, n. 3, p. 1334-1342, 2012

Identificador do objeto digital: 10.1096/fj.11-189969

Descritores: Aedes aegypti - Cell ; Aedes aegypti - Molecular Structure ; Aedes aegypti - Pathogenesis ; Aedes aegypti - Proteins ; Aedes aegypti - RNA ; Aedes aegypti - RT-PCR

Data de publicação: 2012