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An intestinal zinc sensor regulates food intake and developmental growth

Redhai, S.; Pilgrim, C.; Gaspar, P.; Giesen, L. van; Lopes, T.; Riabinina, O.; Grenier, T.; Milona, A.; Chanana, B.; Swadling, J.B.; Wang, Y.-F.; Dahalan, F.; Yuan, M.; Wilsch-Brauninger, M.; Lin, W.-H.; Dennison, N.; Capriotti, P.; Lawniczak, M.K.N.; Baines, R.A.; Warnecke, T.; Windbichler, N.; Leulier, F.; Bellono, N.W.; Miguel-Aliaga, I.

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Authors

S. Redhai

C. Pilgrim

P. Gaspar

L. van Giesen

T. Lopes

T. Grenier

A. Milona

B. Chanana

J.B. Swadling

Y.-F. Wang

F. Dahalan

M. Yuan

M. Wilsch-Brauninger

W.-H. Lin

N. Dennison

P. Capriotti

M.K.N. Lawniczak

R.A. Baines

T. Warnecke

N. Windbichler

F. Leulier

N.W. Bellono

I. Miguel-Aliaga



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.

Citation

Redhai, S., Pilgrim, C., Gaspar, P., Giesen, L. V., Lopes, T., Riabinina, O., …Miguel-Aliaga, I. (2020). An intestinal zinc sensor regulates food intake and developmental growth. Nature, 580(7802), 263-268. https://doi.org/10.1038/s41586-020-2111-5

Journal Article Type Article
Acceptance Date Feb 18, 2020
Online Publication Date Mar 18, 2020
Publication Date 2020
Deposit Date Apr 10, 2020
Publicly Available Date Sep 18, 2020
Journal Nature
Print ISSN 0028-0836
Electronic ISSN 1476-4687
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 580
Issue 7802
Pages 263-268
DOI https://doi.org/10.1038/s41586-020-2111-5

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