title: Identification of two cationic amino acid transporters required for nutritional signaling during mosquito reproduction.
abstract: The defining characteristic of anautogenous mosquitoes is their requirement for a blood meal to initiate reproduction. The need for blood drives the association of vector and host, and is the primary reason why anautogenous mosquitoes are effective disease vectors. During mosquito vitellogenesis, a key process in reproduction, yolk protein precursor (YPP) gene expression is activated specifically in the fat body, the insect analogue of the vertebrate liver. We have demonstrated that blood meal derived amino acids (AAs) activate YPP genes via the target of rapamycin (TOR)-signal transduction pathway. Here we show, by stimulating fat bodies with balanced AA solutions lacking individual AAs, that specific cationic and branched AAs are essential for activation of the vitellogenin (vg) gene, the major YPP gene. Treatment of fat bodies with AA uptake inhibitors results in a strong inhibition of AA-induced vg gene expression proving that an active transport mechanism is necessary to transduce the AA signal. We identified two cationic AA transporters (CATs) in the fat body of Aedes aegypti females--Aa slimfast and iCAT2. RNAi knockdown of slimfast and iCAT2 results in a strong decrease in the response to AAs by the vg gene similar to that seen due to TOR inhibition. These data demonstrate that active uptake of specific AAs plays a key role in nutritional signaling during the onset of vitellogenic gene expression in mosquitoes and it is mediated by two cationic AA transporters.
authors.affiliation: Center for Disease-Vector Research, Department of Entomology and the Institute for Integrative Genome Biology, University of California Riverside, 3401 Watkins Drive, Riverside, CA-92521, USA.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Attardo
authors.forename: Immo A
authors.initials: IA
authors.lastname: Hansen
authors.forename: Shin-Hong
authors.initials: SH
authors.lastname: Shiao
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Raikhel
mesh_terms: D000330:Aedes / Q000378:metabolism* / Q000502:physiology; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism / Q000502:physiology; D000818:Animals; D003001:Cloning, Molecular; D004527:Egg Proteins / Q000235:genetics / Q000378:metabolism; D005216:Fat Body / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012098:Reproduction / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014818:Vitellogenesis / Q000502:physiology
chemical_list: D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids; D004527:Egg Proteins; D019476:Insect Proteins; D011498:Protein Precursors