title: Nutritional and hormonal regulation of the TOR effector 4E-binding protein (4E-BP) in the mosquito Aedes aegypti.
abstract: 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.
authors.affiliation: Department of Entomology, University of California Riverside, 900 University Ave., Riverside, CA 92521, USA.
authors.forename: Saurabh G
authors.initials: SG
authors.lastname: Roy
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Raikhel
mesh_terms: D000330:Aedes / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000494:pharmacology; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001769:Blood; D015153:Blotting, Western; D002867:Chromones / Q000494:pharmacology; D005216:Fat Body / Q000187:drug effects / Q000378:metabolism; D005247:Feeding Behavior; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008136:Longevity / Q000235:genetics; D008969:Molecular Sequence Data; D009025:Morpholines / Q000494:pharmacology; D010063:Ovum / Q000254:growth & development / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D002867:Chromones; D019476:Insect Proteins; D007328:Insulin; D009025:Morpholines; D012097:Repressor Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus