The Nuclear Receptor HIZR-1 Uses Zinc as a Ligand to Mediate Homeostasis in Response to High Zinc

Kurt Warnhoff, Hyun C. Roh, Zuzana Kocsisova, Chieh Hsiang Tan, Andrew Morrison, Damari Croswell, Daniel L. Schneider, Kerry Kornfeld

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Nuclear receptors were originally defined as endocrine sensors in humans, leading to the identification of the nuclear receptor superfamily. Despite intensive efforts, most nuclear receptors have no known ligand, suggesting new ligand classes remain to be discovered. Furthermore, nuclear receptors are encoded in the genomes of primitive organisms that lack endocrine signaling, suggesting the primordial function may have been environmental sensing. Here we describe a novel Caenorhabditis elegans nuclear receptor, HIZR-1, that is a high zinc sensor in an animal and the master regulator of high zinc homeostasis. The essential micronutrient zinc acts as a HIZR-1 ligand, and activated HIZR-1 increases transcription of genes that promote zinc efflux and storage. The results identify zinc as the first inorganic molecule to function as a physiological ligand for a nuclear receptor and direct environmental sensing as a novel function of nuclear receptors.

Original languageEnglish
Article numbere2000094
JournalPLoS biology
Volume15
Issue number1
DOIs
StatePublished - Jan 17 2017

Fingerprint

Dive into the research topics of 'The Nuclear Receptor HIZR-1 Uses Zinc as a Ligand to Mediate Homeostasis in Response to High Zinc'. Together they form a unique fingerprint.

Cite this