Transient expression of the Drosophila melanogaster cinnabar gene rescues eye color in the white eye (WE) strain of Aedes aegypti

Cornel, Anthony J.; Benedict, Mark Q.; Rafferty, Cristina Salazar; Howells, A. J.; Collins, Frank H.

doi:10.1016/s0965-1748(97)00084-2

Cited by 70 publications

(41 citation statements)

References 13 publications

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“…The determination of the kinetic parameters featuring the Ag-HKT-dependent 3-HK transamination revealed that the enzyme is highly active under physiological conditions, thus suggesting a key role of the enzyme in XA biosynthesis in vivo; moreover, the Ag-hkt gene expression profile throughout the lifespan of A. gambiae (21) is in agreement with the proposed 3-HK detoxification activity of the enzyme, confirming earlier observations made in A. aegypti (24). Indeed, the Ag-hkt-specific transcript is abundant in embryos, larvae, and most adult tissues, consistent with the protective role of the enzyme in preventing the 3-HKtriggered oxidative stress response; on the other hand, the observed down-regulation of the Ag-hkt gene transcription in pupae may reflect the physiological 3-HK requirement during compound eye development in the mosquito (25,26) and the potential role of the molecule in insect tissue remodeling during metamorphosis (27). Analyzed in the context of Plasmodium-infected mosquitoes, XA metabolism represents a metabolic crossroad between the biology of the two species promoting malaria spread throughout human populations.…”

supporting

confidence: 89%

Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase

Rossi

Garavaglia²,

Giovenzana³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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In Anopheles gambiae, the vector for the most deadly malaria parasite Plasmodium falciparum, xanthurenic acid (XA) plays a key role in parasite gametogenesis and fertility. In mosquitoes, XA is produced by transamination of 3-hydroxykynurenine (3-HK), a reaction that represents the main route to prevent the accumulation of the potentially toxic 3-HK excess. Interfering with XA metabolism in A. gambiae therefore appears an attractive avenue for the development of malaria transmission-blocking drugs and insecticides. We have determined the crystal structure of A. gambiae 3-HK transaminase in its pyridoxal 5 -phosphate form and in complex with a newly synthesized competitive enzyme inhibitor. Structural inspection of the enzyme active site reveals the key molecular determinants for ligand recognition and catalysis. Major contributions toward inhibitor binding are provided by a salt bridge between the inhibitor carboxylate and Arg-356 and by a remarkable hydrogen bond network involving the anthranilic moiety of the inhibitor and backbone atoms of residues Gly-25 and Asn-44. This study may be useful for the structurebased design of specific enzyme inhibitors of potential interest as antimalarial agents.kynurenine pathway ͉ xanthurenic acid

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supporting

confidence: 89%

Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase

Rossi

Garavaglia²,

Giovenzana³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…In the silkworm, Bombyx mori, mutations in the st ortholog, Bmw-2 (Tatematsu et al 2011), result in white eyes, as do mutations in the enzymes that convert tryptophan to ommochrome pigments (Quan et al 2002). The same is true for the mosquitoes, Anopheles gambia (Benedict et al 1996a;Mukabayire et al 1996) and Aedes aegypti (Cornel et al 1997), as well as the honey bee, Apis mellifera (Dustmann 1968).…”

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confidence: 97%

The ABCs of Eye Color inTribolium castaneum: Orthologs of theDrosophila white,scarlet, andbrownGenes

et al. 2015

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In Drosophila melanogaster, each of the three paralogous ABC transporters, White, Scarlet and Brown, is required for normal pigmentation of the compound eye. We have cloned the three orthologous genes from the beetle Tribolium castaneum. Conceptual translations of Tribolium white (Tcw), scarlet (Tcst), and brown (Tcbw) are 51, 48, and 32% identical to their respective Drosophila counterparts. We have identified loss-of-eye-pigment strains that bear mutations in Tcw and Tcst: the Tcw gene in the ivory (i) strain carries a single-base transversion, which leads to an E / D amino-acid substitution in the highly conserved Walker B motif, while the Tcst gene in the pearl (p) strain has a deletion resulting in incorporation of a premature stop codon. In light of these findings, the mutant strains i and p are herein renamed white ivory (w i ) and scarlet pearl (st p ), respectively. In addition, RNA inhibition of Tcw and Tcst recapitulates the mutant phenotypes, confirming the roles of these genes in normal eye pigmentation, while RNA interference of Tcbw provides further evidence that it has no role in eye pigmentation in Tribolium. We also consider the evolutionary implications of our findings.

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“…This work represents a significant step toward the development of molecular genetic approaches to the control of vector competence in pathogen transmission. The 450-bp coding region of the DefA gene (nucleotides from ϩ50 to ϩ498) (15) was ligated into a BamHI site at the 3Ј-end of a 2.1-kb Vg fragment (nucleotides from Ϫ2,015 to ϩ 70) (9 (20), which is complemented by the D. melanogaster cn gene, which changes the eye color to red (21). The strain was obtained from F. Collins (University of Notre Dame, Notre Dame, IN).…”

mentioning

confidence: 99%

Engineering blood meal-activated systemic immunity in the yellow fever mosquito, Aedes aegypti

Kokoza

Ahmed

Cho

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

168

134

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Progress in molecular genetics makes possible the development of alternative disease control strategies that target the competence of mosquitoes to transmit pathogens. We tested the regulatory region of the vitellogenin (Vg) gene of Aedes aegypti for its ability to express potential antipathogen factors in transgenic mosquitoes. Hermes-mediated transformation was used to integrate a 2.1-kb Vg-promoter fragment driving the expression of the Defensin A (DefA) coding region, one of the major insect immune factors. PCR amplification of genomic DNA and Southern blot analyses, carried out through the ninth generation, showed that the Vg-DefA transgene insertion was stable. The Vg-DefA transgene was strongly activated in the fat body by a blood meal. The mRNA levels reached a maximum at 24-h postblood meal, corresponding to the peak expression time of the endogenous Vg gene. High levels of transgenic defensin were accumulated in the hemolymph of bloodfed female mosquitoes, persisting for 20 -22 days after a single blood feeding. Purified transgenic defensin showed antibacterial activity comparable to that of defensin isolated from bacterially challenged control mosquitoes. Thus, we have been able to engineer the genetically stable transgenic mosquito with an element of systemic immunity, which is activated through the blood meal-triggered cascade rather than by infection. This work represents a significant step toward the development of molecular genetic approaches to the control of vector competence in pathogen transmission.

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Transient expression of the Drosophila melanogaster cinnabar gene rescues eye color in the white eye (WE) strain of Aedes aegypti

Cited by 70 publications

References 13 publications

Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase

Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase

The ABCs of Eye Color inTribolium castaneum: Orthologs of theDrosophila white,scarlet, andbrownGenes

Engineering blood meal-activated systemic immunity in the yellow fever mosquito, Aedes aegypti

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