Auxin confers protection against ER stress in <i>Caenorhabditis elegans</i>

Bhoi, Anupam; Palladino, Francesca; Fabrizio, Paola

doi:10.1101/2020.11.15.383760

Cited by 7 publications

(14 citation statements)

References 35 publications

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“…The different strains underwent larval development normally and we were able to maintain them under standard culture conditions. Except when amplifying large populations for biochemistry (see Methods , and below), we therefore conducted experiments on worms that had not been exposed to auxin, avoiding its possible confounding side effects [ 38 ]. After the 4 th larval stage (L4) to adult moult, coincident with the increasing activity of the col-19 promoter, fluorescence from the chimeric proteins started to be visible.…”

Section: Resultsmentioning

confidence: 99%

Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences

Zhang

Harding²,

Aggad³

et al. 2021

PLoS Genet

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Animals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second increases STA-2 levels in the nucleus, modifies the nucleolus, and, potentially as a consequence of a host surveillance mechanism, causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens.

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Section: Resultsmentioning

confidence: 99%

Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences

Zhang

Harding²,

Aggad³

et al. 2021

PLoS Genet

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show abstract

“…In all cases, we were able to maintain viable strains under standard culture conditions. In subsequent experiments, we therefore conducted experiments on worms that had not been exposed to auxin, avoiding its possible confounding side-effects (Bhoi et al, 2020), and concentrated principally on the characterisation of DcEntA and DcEntB. Upon normal handling, adult DcEntA-expressing worms, but not DcEntB-expressing worms, appeared more prone to break apart.…”

Section: Resultsmentioning

confidence: 99%

Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences

Zhang

Harding

Aggad

et al. 2020

Preprint

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Animals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second, potentially as a consequence of a host surveillance mechanism, increases STA-2 levels in the nucleus, modifies the nucleolus, and causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens.

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“…Most AID experiments in C. elegans use concentrations of auxin around 1 mM. At this high of a concentration, auxin alone has effects on the animals such as promoting ER stress resistance 19 . To avoid this and any other potential side effects of high auxin concentrations, we performed an auxin concentration gradient experiment to find a low dose that was sufficient to induce degradation of an AID-tagged protein but without any effect on lifespan.…”

Section: Efficient Degradation Is Achieved At a Low Auxin Concentration That Minimizes Off-target Effectsmentioning

confidence: 99%

Neuronal mTORC1 inhibition promotes longevity without suppressing anabolic growth and reproduction inC. elegans

Smith

Lanjuin

Sharma

et al. 2021

Preprint

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One of the most robust and reproducible methods to prolong lifespan in a variety of organisms is inhibition of the mTORC1 (mechanistic target of rapamycin complex 1) pathway. mTORC1 is a metabolic sensor that promotes anabolic growth when nutrients are abundant. Inhibition of mTORC1 extends lifespan, but also frequently has other effects such as stunted growth, slowed development, reduced fertility, and disrupted metabolism. It has long been assumed that suppression of anabolism and resulting phenotypes such as impaired growth and reproduction may be causal to mTORC1 longevity, but this hypothesis has not been directly tested. RAGA-1 is an upstream activator of TORC1. Previous work from our lab using a C. elegans model of mTORC1 longevity, the long-lived raga-1 null mutant, found that the presence of RAGA-1 only in the neurons suppresses longevity of the null mutant. Here, we use the auxin-inducible degradation (AID) system to test whether neuronal mTORC1 inhibition is sufficient for longevity, and whether any changes in lifespan are also linked to stunted growth or fertility. We find that life-long AID of RAGA-1 either in all somatic tissue or only in the neurons of C. elegans is sufficient to extend lifespan. We also find that AID of RAGA-1 or LET-363/mTOR beginning at day 1 of adulthood extends lifespan to a similar extent. Unlike somatic degradation of RAGA-1, neuronal degradation of RAGA-1 does not impair growth, slow development, or decrease the reproductive capacity of the worms. Lastly, while AID of LET-363/mTOR in all somatic cells shortens lifespan, neuronal AID of LET-363/mTOR promotes longevity. This work demonstrates that targeting mTORC1 specifically in the neurons uncouples longevity from growth and reproductive impairments, challenging previously held ideas about the mechanisms of mTORC1 longevity and elucidating the promise of tissue-specific aging therapeutics.

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Auxin confers protection against ER stress in Caenorhabditis elegans

Cited by 7 publications

References 35 publications

Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences

Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences

Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences

Neuronal mTORC1 inhibition promotes longevity without suppressing anabolic growth and reproduction inC. elegans

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