Behavioral decline and premature lethality upon pan-neuronal ferritin overexpression in Drosophila infected with a virulent form of Wolbachia

Kosmidis, Stylianos; Missirlis, Fanis; Botella, J; Schneuwly, Stephan; Rouault, Tracey A.; Skoulakis, Efthimios M. C.

doi:10.3389/fphar.2014.00066

Cited by 22 publications

(13 citation statements)

References 34 publications

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“…Two further Fer2LCH-Gal4 lines became available from the Kyoto stock center [ 70 ] and all three lines gave identical intestinal expression. Ferritin is also expressed in the brain [ 10 , 24 , 71 , 72 , 73 , 74 , 75 ]. Images obtained from the brains indicated some differences between the three Fer2LCH-Gal4 lines, but these results are not presented here.…”

Section: Resultsmentioning

confidence: 99%

Ferritin Assembly in Enterocytes of Drosophila melanogaster

Rosas‐Arellano

Vásquez-Procopio

Gambis

et al. 2016

IJMS

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Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH) and Ferritin 2 Light Chain Homolog (Fer2LCH) are further stabilized by disulfide-bridge in the 24-subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH-Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated.

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Section: Resultsmentioning

confidence: 99%

Ferritin Assembly in Enterocytes of Drosophila melanogaster

Rosas‐Arellano

Vásquez-Procopio

Gambis

et al. 2016

IJMS

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“…While neither assay made a direct comparison of these traits between Wolbachia -infected and -uninfected A. aegypti , the difference in results could suggest that egg production in Wolbachia -infected A. aegypti differs from in uninfected mosquitoes. Wolbachia -iron interactions appear to be a key component of the Wolbachia -host relationship, with Wolbachia exhibiting a requirement for iron, altering oxidative stress response in mosquitoes, and increasing host tolerance to iron toxicity 19 , 27 – 29 . Our results here could be a further example of this metabolic relationship.…”

Section: Discussionmentioning

confidence: 99%

Development and physiological effects of an artificial diet for Wolbachia-infected Aedes aegypti

Dutra

Rodrigues

Mansur

et al. 2017

Sci Rep

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The endosymbiotic bacterium Wolbachia spreads rapidly through populations of Aedes aegypti mosquitoes, and strongly inhibits infection with key human pathogens including the dengue and Zika viruses. Mosquito control programs aimed at limiting transmission of these viruses are ongoing in multiple countries, yet there is a dearth of mass rearing infrastructure specific to Wolbachia-infected mosquitoes. One example is the lack of a blood meal substitute, which accounts for the Wolbachia-specific physiological changes in infected mosquitoes, that allows the bacterium to spread, and block viral infections. To that end, we have developed a blood meal substitute specifically for mosquitoes infected with the wMel Wolbachia strain. This diet, ADM, contains milk protein, and infant formula, dissolved in a mixture of bovine red blood cells and Aedes physiological saline, with ATP as a phagostimulant. Feeding with ADM leads to high levels of viable egg production, but also does not affect key Wolbachia parameters including, bacterial density, cytoplasmic incompatibility, or resistance to infection with Zika virus. ADM represents an effective substitute for human blood, which could potentially be used for the mass rearing of wMel-infected A. aegypti, and could easily be optimized in the future to improve performance.

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“…Furthermore, some cell types, including commonly used cell culture lines [ 55 , 56 ], only express Fer1HCH and not Fer2LCH . Overexpression of either Fer1HCH or Fer2LCH , or both subunits simultaneously in Drosophila glia [ 43 ] or neurons [ 53 , 57 ] resulted in qualitatively different responses. We also find that embryonic ectopic expression of both ferritin subunits leads to some cells differentially expressing one of the two genes.…”

Section: Discussionmentioning

confidence: 99%

Ferritin Is Required in Multiple Tissues during Drosophila melanogaster Development

et al. 2015

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In Drosophila melanogaster, iron is stored in the cellular endomembrane system inside a protein cage formed by 24 ferritin subunits of two types (Fer1HCH and Fer2LCH) in a 1:1 stoichiometry. In larvae, ferritin accumulates in the midgut, hemolymph, garland, pericardial cells and in the nervous system. Here we present analyses of embryonic phenotypes for mutations in Fer1HCH, Fer2LCH and in both genes simultaneously. Mutations in either gene or deletion of both genes results in a similar set of cuticular embryonic phenotypes, ranging from non-deposition of cuticle to defects associated with germ band retraction, dorsal closure and head involution. A fraction of ferritin mutants have embryonic nervous systems with ventral nerve cord disruptions, misguided axonal projections and brain malformations. Ferritin mutants die with ectopic apoptotic events. Furthermore, we show that ferritin maternal contribution, which varies reflecting the mother’s iron stores, is used in early development. We also evaluated phenotypes arising from the blockage of COPII transport from the endoplasmic reticulum to the Golgi apparatus, feeding the secretory pathway, plus analysis of ectopically expressed and fluorescently marked Fer1HCH and Fer2LCH. Overall, our results are consistent with insect ferritin combining three functions: iron storage, intercellular iron transport, and protection from iron-induced oxidative stress. These functions are required in multiple tissues during Drosophila embryonic development.

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Behavioral decline and premature lethality upon pan-neuronal ferritin overexpression in Drosophila infected with a virulent form of Wolbachia

Cited by 22 publications

References 34 publications

Ferritin Assembly in Enterocytes of Drosophila melanogaster

Ferritin Assembly in Enterocytes of Drosophila melanogaster

Development and physiological effects of an artificial diet for Wolbachia-infected Aedes aegypti

Ferritin Is Required in Multiple Tissues during Drosophila melanogaster Development

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