RRC ID 59034
Author 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.
Title An intestinal zinc sensor regulates food intake and developmental growth.
Journal Nature
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.
Volume 580(7802)
Pages 263-268
Published 2020-4-1
DOI 10.1038/s41586-020-2111-5
PII 10.1038/s41586-020-2111-5
PMID 32269334
MeSH Animals Chloride Channels / metabolism* Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development* Drosophila melanogaster / metabolism* Eating / physiology* Enterocytes / metabolism Female Food Preferences Homeostasis Insect Vectors Insulin / metabolism Intestines / physiology* Ion Channel Gating Larva / genetics Larva / growth & development Larva / metabolism Lysosomes / metabolism Male Oocytes / metabolism Receptor Protein-Tyrosine Kinases / metabolism Signal Transduction Xenopus Zinc / metabolism*
IF 42.779
Times Cited 5
Drosophila 11340R-3 DGRC#113517 DGRC#112001 DGRC#110620 DGRC#110558