Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
An intestinal zinc sensor regulates food intake and developmental growth.
Redhai S
,
Pilgrim C
,
Gaspar P
,
Giesen LV
,
Lopes T
,
Riabinina O
,
Grenier T
,
Milona A
,
Chanana B
,
Swadling JB
,
Wang YF
,
Dahalan F
,
Yuan M
,
Wilsch-Brauninger M
,
Lin WH
,
Dennison N
,
Capriotti P
,
Lawniczak MKN
,
Baines RA
,
Warnecke T
,
Windbichler N
,
Leulier F
,
Bellono NW
,
Miguel-Aliaga I
.
???displayArticle.abstract???
In cells, organs and whole organisms, nutrient sensing is key to maintaining homeostasis and adapting to a fluctuating environment1. In many animals, nutrient sensors are found within the enteroendocrine cells of the digestive system; however, less is known about nutrient sensing in their cellular siblings, the absorptive enterocytes1. Here we use a genetic screen in Drosophila melanogaster to identify Hodor, an ionotropic receptor in enterocytes that sustains larval development, particularly in nutrient-scarce conditions. Experiments in Xenopus oocytes and flies indicate that Hodor is a pH-sensitive, zinc-gated chloride channel that mediates a previously unrecognized dietary preference for zinc. Hodor controls systemic growth from a subset of enterocytes-interstitial cells-by promoting food intake and insulin/IGF signalling. Although Hodor sustains gut luminal acidity and restrains microbial loads, its effect on systemic growth results from the modulation of Tor signalling and lysosomal homeostasis within interstitial cells. Hodor-like genes are insect-specific, and may represent targets for the control of disease vectors. Indeed, CRISPR-Cas9 genome editing revealed that the single hodor orthologue in Anopheles gambiae is an essential gene. Our findings highlight the need to consider the instructive contributions of metals-and, more generally, micronutrients-to energy homeostasis.
,
Errors in babies' food.
1970,
Pubmed
Axelsson,
Genome sequence of the naturally plasmid-free Lactobacillus plantarum strain NC8 (CCUG 61730).
2012,
Pubmed
Baena-Lopez,
Accelerated homologous recombination and subsequent genome modification in Drosophila.
2013,
Pubmed
Baker,
A comprehensive gene expression atlas of sex- and tissue-specificity in the malaria vector, Anopheles gambiae.
2011,
Pubmed
Bhatt,
Functional analysis of the larval feeding circuit in Drosophila.
2013,
Pubmed
Bischof,
An optimized transgenesis system for Drosophila using germ-line-specific phiC31 integrases.
2007,
Pubmed
Blaby-Haas,
Lysosome-related organelles as mediators of metal homeostasis.
2014,
Pubmed
Colombani,
A nutrient sensor mechanism controls Drosophila growth.
2003,
Pubmed
Cong,
Multiplex genome engineering using CRISPR/Cas systems.
2013,
Pubmed
Cooper,
Sch 36605, structure of a novel nucleoside.
1988,
Pubmed
Dent,
Evidence for a diverse Cys-loop ligand-gated ion channel superfamily in early bilateria.
2006,
Pubmed
Dubreuil,
Mutations of alpha spectrin and labial block cuprophilic cell differentiation and acid secretion in the middle midgut of Drosophila larvae.
1998,
Pubmed
Erkosar,
Drosophila microbiota modulates host metabolic gene expression via IMD/NF-κB signaling.
2014,
Pubmed
Feingold,
The orphan pentameric ligand-gated ion channel pHCl-2 is gated by pH and regulates fluid secretion in Drosophila Malpighian tubules.
2016,
Pubmed
Filshie,
Ultrastructure of the copper-accumulating region of the Drosophila larval midgut.
1971,
Pubmed
Géminard,
Remote control of insulin secretion by fat cells in Drosophila.
2009,
Pubmed
Goldsmith,
Cardiologists send up a trial balloon in new efforts to relieve heart failure.
1987,
Pubmed
González,
Nutrient sensing and TOR signaling in yeast and mammals.
2017,
Pubmed
Hammond,
A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae.
2016,
Pubmed
Hegedűs,
The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy.
2016,
Pubmed
Hervas,
PopFly: the Drosophila population genomics browser.
2017,
Pubmed
Holly,
Paneth Cells during Viral Infection and Pathogenesis.
2018,
Pubmed
Hudry,
Sex Differences in Intestinal Carbohydrate Metabolism Promote Food Intake and Sperm Maturation.
2019,
Pubmed
Kakanj,
Insulin and TOR signal in parallel through FOXO and S6K to promote epithelial wound healing.
2016,
Pubmed
Kim,
Regulation of TORC1 by Rag GTPases in nutrient response.
2008,
Pubmed
Kriventseva,
OrthoDB v10: sampling the diversity of animal, plant, fungal, protist, bacterial and viral genomes for evolutionary and functional annotations of orthologs.
2019,
Pubmed
Larkin,
Clustal W and Clustal X version 2.0.
2007,
Pubmed
Layalle,
The TOR pathway couples nutrition and developmental timing in Drosophila.
2008,
Pubmed
Li,
Unbiased estimation of the rates of synonymous and nonsynonymous substitution.
1993,
Pubmed
Li,
Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.
2016,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Lin,
MIB: Metal Ion-Binding Site Prediction and Docking Server.
2016,
Pubmed
Maier,
ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB.
2015,
Pubmed
Marois,
The endocytic pathway and formation of the Wingless morphogen gradient.
2006,
Pubmed
Mauvezin,
Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion.
2015,
Pubmed
Miguel-Aliaga,
Nerveless and gutsy: intestinal nutrient sensing from invertebrates to humans.
2012,
Pubmed
Miller,
MMPBSA.py: An Efficient Program for End-State Free Energy Calculations.
2012,
Pubmed
Misof,
Phylogenomics resolves the timing and pattern of insect evolution.
2014,
Pubmed
Musselman,
A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila.
2011,
Pubmed
Negi,
LocSigDB: a database of protein localization signals.
2015,
Pubmed
Overend,
Molecular mechanism and functional significance of acid generation in the Drosophila midgut.
2016,
Pubmed
Park,
Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut.
2019,
Pubmed
Pfeifer,
PopGenome: an efficient Swiss army knife for population genomic analyses in R.
2014,
Pubmed
Phillips,
Brush border spectrin is required for early endosome recycling in Drosophila.
2006,
Pubmed
Pircs,
Advantages and limitations of different p62-based assays for estimating autophagic activity in Drosophila.
2012,
Pubmed
Preibisch,
Globally optimal stitching of tiled 3D microscopic image acquisitions.
2009,
Pubmed
Remnant,
Evolution, Expression, and Function of Nonneuronal Ligand-Gated Chloride Channels in Drosophila melanogaster.
2016,
Pubmed
Rera,
Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog.
2011,
Pubmed
Robert,
Deciphering key features in protein structures with the new ENDscript server.
2014,
Pubmed
Robinson,
Integrative genomics viewer.
2011,
Pubmed
Rodenfels,
Production of systemically circulating Hedgehog by the intestine couples nutrition to growth and development.
2014,
Pubmed
Roh,
Lysosome-related organelles in intestinal cells are a zinc storage site in C. elegans.
2012,
Pubmed
Romero-Pozuelo,
CycD/Cdk4 and Discontinuities in Dpp Signaling Activate TORC1 in the Drosophila Wing Disc.
2017,
Pubmed
Rulifson,
Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes.
2002,
Pubmed
Sancak,
Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.
2010,
Pubmed
Saxton,
mTOR Signaling in Growth, Metabolism, and Disease.
2017,
Pubmed
Schindelin,
Fiji: an open-source platform for biological-image analysis.
2012,
Pubmed
Şentürk,
Ubiquilins regulate autophagic flux through mTOR signalling and lysosomal acidification.
2019,
Pubmed
Shen,
Analysis of feeding behavior of Drosophila larvae on solid food.
2012,
Pubmed
Shin,
Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling.
2011,
Pubmed
Storelli,
Lactobacillus plantarum promotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing.
2011,
Pubmed
Storelli,
Drosophila Perpetuates Nutritional Mutualism by Promoting the Fitness of Its Intestinal Symbiont Lactobacillus plantarum.
2018,
Pubmed
Sudarsan,
A genetic hierarchy establishes mitogenic signalling and mitotic competence in the renal tubules of Drosophila.
2002,
Pubmed
Sun,
Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian Tubule.
2018,
Pubmed
Toshima,
Taste preference for amino acids is dependent on internal nutritional state in Drosophila melanogaster.
2012,
Pubmed
Valvezan,
Molecular logic of mTORC1 signalling as a metabolic rheostat.
2019,
Pubmed
Volohonsky,
Tools for Anopheles gambiae Transgenesis.
2015,
Pubmed
Wertheim,
RELAX: detecting relaxed selection in a phylogenetic framework.
2015,
Pubmed
Zoncu,
mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase.
2011,
Pubmed
