Newly Identified Nematodes from Mono Lake Exhibit Extreme Arsenic Resistance

Shih, Pei-Yin; Lee, James Siho; Shinya, Ryoji; Kanzaki, Natsumi; Pires-daSilva, André; Badroos, Jean M; Goetz, Elizabeth M.; Sapir, Amir; Sternberg, Paul W.

doi:10.1016/j.cub.2019.08.024

“…This suggests a critical physiological role of ogt-1 in the ability of C . elegans to survive in the wild, since worms are continuously exposed to fluctuating environmental salinity in their native ecosystems [ 42 ]. Given that both C .…”

Section: Discussionmentioning

confidence: 99%

“…Such conditions have minimal effects on the ability of wild type animals to adapt and develop [10]. This suggests a critical physiological role of ogt-1 in the ability of C. elegans to survive in the wild, since worms are continuously exposed to fluctuating environmental salinity in their native ecosystems [42]. Given that both C. elegans and human OGT are able to rescue the Nio phenotype of ogt-1 mutants in C. elegans, we speculate that OGT plays an ancient and conserved physiological function in response to environmental and physiological perturbations in osmotic homeostasis.…”

Section: Plos Geneticsmentioning

confidence: 99%

The O-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress

Urso

¹

,

Comly

²

,

Hanover

³

et al. 2020

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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.

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“…Such conditions have minimal effects on the ability of wild type animals to adapt and reproduce (10). This suggests a critical physiological role of ogt-1 in the ability of C. elegans to survive in the wild, since worms are continuously exposed to fluctuating environmental salinity in their native ecosystems (37). Given that both C. elegans and human OGT are able to rescue the Nio phenotype of ogt-1 mutants in C. elegans, we speculate that OGT plays an ancient and conserved physiological function in response to environmental and physiological perturbations in osmotic homeostasis.…”

mentioning

confidence: 99%

TheO-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress

Urso

¹

,

Comly

²

,

Hanover

³

et al. 2020

Preprint

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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, mutations that ablate O-GlcNAcylation activity in either human or C. elegansOGT rescue the hypertonic stress response phenotype. 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. Author SummaryThe ability to sense and adapt to changes in the environment is an essential feature of cellular life. Changes in environmental salt and water concentrations can rapidly cause cell volume swelling or shrinkage and, if left unchecked, will lead to cell and organismal death. All organisms have developed similar physiological strategies for maintaining cell volume. However, the molecular mechanisms that control these physiological outputs are not well understood in animals. Using unbiased genetic screening in C. elegans, we discovered that a highly conserved enzyme called O-GlcNAc transferase (OGT) is essential for regulating physiological responses to increased environmental solute levels. A human form of OGT can functionally substitute for worm OGT, showing that this role is conserved across evolution. Surprisingly, the only known enzymatic activity of OGT was not required for this role, suggesting this enzyme has important undescribed molecular functions. Our studies reveal a new animal-specific role for OGT in the response to osmotic stress and show that C. elegans is an important model for defining the conserved molecular mechanisms that respond to alterations in cell volume.

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“…Changes in environmental conditions may then lead to selection and fixation of cryptic variants, resulting in rapid DSD (Johnson and Porter, 2007;Duveau and Félix, 2012). By availing of nematodes isolated from diverse geographical locations, including those from extreme habitats (Shih et al, 2019), it will be of interest to ask how environment cues shape the endoderm GRN structure.…”

Section: Resultsmentioning

confidence: 99%

Evolution and Developmental System Drift in the Endoderm Gene Regulatory Network of Caenorhabditis and Other Nematodes

Ewe

¹

,

Cleuren

²

,

Rothman

³

2020

Front. Cell Dev. Biol.

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Developmental gene regulatory networks (GRNs) underpin metazoan embryogenesis and have undergone substantial modification to generate the tremendous variety of animal forms present on Earth today. The nematode Caenorhabditis elegans has been a central model for advancing many important discoveries in fundamental mechanistic biology and, more recently, has provided a strong base from which to explore the evolutionary diversification of GRN architecture and developmental processes in other species. In this short review, we will focus on evolutionary diversification of the GRN for the most ancient of the embryonic germ layers, the endoderm. Early embryogenesis diverges considerably across the phylum Nematoda. Notably, while some species deploy regulative development, more derived species, such as C. elegans, exhibit largely mosaic modes of embryogenesis. Despite the relatively similar morphology of the nematode gut across species, widespread variation has been observed in the signaling inputs that initiate the endoderm GRN, an exemplar of developmental system drift (DSD). We will explore how genetic variation in the endoderm GRN helps to drive DSD at both inter-and intraspecies levels, thereby resulting in a robust developmental system. Comparative studies using divergent nematodes promise to unveil the genetic mechanisms controlling developmental plasticity and provide a paradigm for the principles governing evolutionary modification of an embryonic GRN.

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Newly Identified Nematodes from Mono Lake Exhibit Extreme Arsenic Resistance

Cited by 26 publications

References 35 publications

The O-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress

The O-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress

TheO-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress

Evolution and Developmental System Drift in the Endoderm Gene Regulatory Network of Caenorhabditis and Other Nematodes

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