title: Ferritin Assembly in Enterocytes of Drosophila melanogaster.
abstract: 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.
authors: Department of Physiology, Biophysics and Neuroscience, Cinvestav del IPN, Avenida IPN 2508, Zacatenco, Mexico City 07360, Mexico. rosas.arellano@gmail.com.
authors: Abraham
authors: A
authors: Rosas-Arellano
authors: Department of Physiology, Biophysics and Neuroscience, Cinvestav del IPN, Avenida IPN 2508, Zacatenco, Mexico City 07360, Mexico. yo-ana3@hotmail.com.
authors: Johana
authors: J
authors: Vásquez-Procopio
authors: Howard Hughes Medical Institute, Strang Laboratory of Apoptosis and Cancer, The Rockefeller University, New York, NY 10065, USA. agambis@gmail.com.
authors: Alexis
authors: A
authors: Gambis
authors: Department of Organismal Biology, School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK. l.m.blowes@qmul.ac.uk.
authors: Liisa M
authors: LM
authors: Blowes
authors: Howard Hughes Medical Institute, Strang Laboratory of Apoptosis and Cancer, The Rockefeller University, New York, NY 10065, USA. steller@mail.rockefeller.edu.
authors: Hermann
authors: H
authors: Steller
authors: Laboratory of Molecular Biology of the Cell, UMR5239 CNRS/Ecole Normale Supérieure de Lyon, IFR 128 Biosciences Lyon Gerland, Université de Lyon, Lyon 69007, France. Bertrand.Mollereau@ens-lyon.fr.
authors: Bertrand
authors: B
authors: Mollereau
authors: Department of Physiology, Biophysics and Neuroscience, Cinvestav del IPN, Avenida IPN 2508, Zacatenco, Mexico City 07360, Mexico. fanis@fisio.cinvestav.mx.
authors: Fanis
authors: F
authors: Missirlis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism*; D005293:Ferritins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D005838:Genotype; D007501:Iron / Q000378:metabolism; D007814:Larva; D008954:Models, Biological; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins
chemical_list: D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D005293:Ferritins; D007501:Iron
keywords: biosynthesis; complex formation; confocal microscopy; enterocyte; feedback control; insect; iron; metal; midgut; vesicular traffic