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Nutritional and hormonal regulation of the TOR effector 4E‐binding protein (4E‐BP) in the mosquito Aedes aegypti
Author(s) -
Roy Saurabh G.,
Raikhel Alexander S.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-189969
Subject(s) - phosphorylation , biology , aedes aegypti , pi3k/akt/mtor pathway , effector , microbiology and biotechnology , translational regulation , signal transduction , translation (biology) , gene , messenger rna , biochemistry , ecology , larva
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.—Roy, S. G., Raikhel, A. S. Nutritional and hormonal regulation of the TOR effector 4E‐binding protein (4E‐BP) in the mosquito Aedes aegypti. FASEB J. 26, 1334‐1342 (2012). www.fasebj.org