The O-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress
Autoři:
Sarel J. Urso aff001; Marcella Comly aff003; John A. Hanover aff003; Todd Lamitina aff001
Působiště autorů:
Graduate Program in Cell Biology and Molecular Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
aff001; Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
aff002; Laboratory of Cellular and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, MD, United States of America
aff003; Division of Child Neurology, Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States of America
aff004
Vyšlo v časopise:
The O-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1008821
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008821
Souhrn
The conserved O-GlcNAc transferase OGT O-GlcNAcylates serine and threonine residues of intracellular proteins to regulate their function. OGT is required for viability in mammalian cells, but its specific roles in cellular physiology are poorly understood. Here we describe a conserved requirement for OGT in an essential aspect of cell physiology: the hypertonic stress response. Through a forward genetic screen in Caenorhabditis elegans, we discovered OGT is acutely required for osmoprotective protein expression and adaptation to hypertonic stress. Gene expression analysis shows that ogt-1 functions through a post-transcriptional mechanism. Human OGT partially rescues the C. elegans phenotypes, suggesting that the osmoregulatory functions of OGT are ancient. Intriguingly, expression of O-GlcNAcylation-deficient forms of human or worm OGT rescue the hypertonic stress response phenotype. However, expression of an OGT protein lacking the tetracopeptide repeat (TPR) domain does not rescue. Our findings are among the first to demonstrate a specific physiological role for OGT at the organismal level and demonstrate that OGT engages in important molecular functions outside of its well described roles in post-translational O-GlcNAcylation of intracellular proteins.
Klíčová slova:
Alleles – Caenorhabditis elegans – CRISPR – Fluorescence microscopy – Genetic screens – Osmotic shock – RNA interference – Hypertonic
Zdroje
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