General control nonderepressible 1 interacts with cationic amino acid transporter 1 and affects Aedes aegypti fecundity

Parasit Vectors. 2022 Oct 21;15(1):383. doi: 10.1186/s13071-022-05461-x.

Abstract

Background: The amino acid transporter protein cationic amino acid transporter 1 (CAT1) is part of the nutrient sensor in the fat body of mosquitoes. A member of the SLC7 family of cationic amino acid transporters, it is paramount for the detection of elevated amino acid levels in the mosquito hemolymph after a blood meal and the subsequent changes in gene expression in the fat body.

Methods: We performed a re-annotation of Aedes aegypti cationic amino acid transporters (CATs) and selected the C-terminal tail of CAT1 to perform a yeast two-hybrid screen to identify putative interactors of this protein. One interesting interacting protein we identified was general control nonderepressible 1 (GCN1). We determined the expression pattern of GCN1 in several adult organs and structures using qRT-PCR and western blots. Finally, we knocked down GCN1 using double-stranded RNA and identified changes in downstream signaling intermediates and the effects of knockdown on vitellogenesis and fecundity.

Results: In a screen for Ae. aegypti CAT1-interacting proteins we identified GCN1 as a putative interactor. GCN1 is highly expressed in the ovaries and fat body of the mosquito. We provide evidence that eukaryotic translation initiation factor 2 subunit alpha (eIF2α) phosphorylation changed during vitellogenesis and that RNA interference knockdown of GCN1 in whole mosquitoes reduced egg clutch sizes of treated mosquitoes relative to controls.

Conclusions: Aedes aegypti CAT1 and GCN1 are likely interacting partners and GCN1 is likely necessary for proper egg development. Our data suggest that GCN1 is part of a nutrient sensor mechanism in various mosquito tissues involved in vitellogenesis.

Keywords: Aedes; Amino acid transport; Cationic amino acid transporter 1; Fat body; GCN1; Nutrient sensor.

MeSH terms

  • Aedes* / genetics
  • Aedes* / metabolism
  • Amino Acid Transport Systems, Basic / genetics
  • Amino Acid Transport Systems, Basic / metabolism
  • Amino Acids / genetics
  • Animals
  • Cationic Amino Acid Transporter 1 / genetics
  • Cationic Amino Acid Transporter 1 / metabolism
  • Fertility
  • Prokaryotic Initiation Factor-2 / genetics
  • Prokaryotic Initiation Factor-2 / metabolism
  • RNA, Double-Stranded / metabolism
  • Saccharomyces cerevisiae / genetics

Substances

  • Cationic Amino Acid Transporter 1
  • RNA, Double-Stranded
  • Prokaryotic Initiation Factor-2
  • Amino Acid Transport Systems, Basic
  • Amino Acids