Caenorhabditis elegans utilizes dauer pheromone biosynthesis to dispose of toxic peroxisomal fatty acids for cellular homoeostasis

2009 ◽  
Vol 422 (1) ◽  
pp. 61-71 ◽  
Author(s):  
Hyoe-Jin Joo ◽  
Yong-Hyeon Yim ◽  
Pan-Young Jeong ◽  
You-Xun Jin ◽  
Jeong-Eui Lee ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Caenorhabditis Elegans ◽  
Fatty Acyl ◽  
Pheromone Biosynthesis ◽  
Side Chain ◽  
Term Survival ◽  
Developmental Defects ◽  
C Elegans ◽  
Massive Accumulation

Caenorhabditis elegans excretes a dauer pheromone or daumone composed of ascarylose and a fatty acid side chain, the perception of which enables worms to enter the dauer state for long-term survival in an adverse environment. During the course of elucidation of the daumone biosynthetic pathway in which DHS-28 and DAF-22 are involved in peroxisomal β-oxidation of VLCFAs (very long-chain fatty acids), we sought to investigate the physiological consequences of a deficiency in daumone biosynthesis in C. elegans. Our results revealed that two mutants, dhs-28(tm2581) and daf-22(ok693), lacked daumones and thus were dauer defective; this coincided with massive accumulation of fatty acyl-CoAs (up to 100-fold) inside worm bodies compared with levels in wild-type N2 worms. Furthermore, the deficiency in daumone biosynthesis and the massive accumulation of fatty acids and their acyl-CoAs caused severe developmental defects with reduced life spans (up to 30%), suggesting that daumone biosynthesis is be an essential part of C. elegans homoeostasis, affecting survival and maintenance of optimal physiological conditions by metabolizing some of the toxic non-permissible peroxisomal VLCFAs from the worm body in the form of readily excretable daumones.

scholarly journals Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans

2015 ◽  
Vol 112 (13) ◽  
pp. 3955-3960 ◽  
Author(s):  
Xinxing Zhang ◽  
Likui Feng ◽  
Satya Chinta ◽  
Prashant Singh ◽  
Yuting Wang ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Environmental Conditions ◽  
Side Chain ◽  
Side Chains ◽  
Activity Assay ◽  
C Elegans ◽  
Substrate Preferences ◽  
Acyl Coa Oxidase ◽  
Coa Thioesters

Caenorhabditis elegans uses ascaroside pheromones to induce development of the stress-resistant dauer larval stage and to coordinate various behaviors. Peroxisomal β-oxidation cycles are required for the biosynthesis of the fatty acid-derived side chains of the ascarosides. Here we show that three acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, form different protein homo- and heterodimers with distinct substrate preferences. Mutations in the acyl-CoA oxidase genes acox-1, -2, and -3 led to specific defects in ascaroside production. When the acyl-CoA oxidases were expressed alone or in pairs and purified, the resulting acyl-CoA oxidase homo- and heterodimers displayed different side-chain length preferences in an in vitro activity assay. Specifically, an ACOX-1 homodimer controls the production of ascarosides with side chains with nine or fewer carbons, an ACOX-1/ACOX-3 heterodimer controls the production of those with side chains with seven or fewer carbons, and an ACOX-2 homodimer controls the production of those with ω-side chains with less than five carbons. Our results support a biosynthetic model in which β-oxidation enzymes act directly on the CoA-thioesters of ascaroside biosynthetic precursors. Furthermore, we identify environmental conditions, including high temperature and low food availability, that induce the expression of acox-2 and/or acox-3 and lead to corresponding changes in ascaroside production. Thus, our work uncovers an important mechanism by which C. elegans increases the production of the most potent dauer pheromones, those with the shortest side chains, under specific environmental conditions.

scholarly journals A novel member of the GCN5-related N-acetyltransferase superfamily from Caenorhabditis elegans preferentially catalyses the N-acetylation of thialysine [S-(2-aminoethyl)-L-cysteine]

2004 ◽  
Vol 384 (1) ◽  
pp. 129-137 ◽  
Author(s):  
Benjamin ABO-DALO ◽  
Dieudonne NDJONKA ◽  
Francesco PINNEN ◽  
Eva LIEBAU ◽  
Kai LÜERSEN
Keyword(s):  
Caenorhabditis Elegans ◽  
Reversed Phase ◽  
Open Reading Frame ◽  
Side Chain ◽  
Homologous Gene ◽  
Reversed Phase Hplc ◽  
Nematode Caenorhabditis Elegans ◽  
Reading Frame ◽  
Considerable Similarity ◽  
C Elegans

The putative diamine N-acetyltransferase D2023.4 has been cloned from the model nematode Caenorhabditis elegans. The 483 bp open reading frame of the cDNA encodes a deduced polypeptide of 18.6 kDa. Accordingly, the recombinantly expressed His6-tagged protein forms an enzymically active homodimer with a molecular mass of approx. 44000 Da. The protein belongs to the GNAT (GCN5-related N-acetyltransferase) superfamily, and its amino acid sequence exhibits considerable similarity to mammalian spermidine/spermine-N1-acetyltransferases. However, neither the polyamines spermidine and spermine nor the diamines putrescine and cadaverine were efficiently acetylated by the protein. The smaller diamines diaminopropane and ethylenediamine, as well as L-lysine, represent better substrates, but, surprisingly, the enzyme most efficiently catalyses the N-acetylation of amino acids analogous with L-lysine. As determined by the kcat/Km values, the C. elegans N-acetyltransferase prefers thialysine [S-(2-aminoethyl)-L-cysteine], followed by O-(2-aminoethyl)-L-serine and S-(2-aminoethyl)-D,L-homocysteine. Reversed-phase HPLC and mass spectrometric analyses revealed that N-acetylation of L-lysine and L-thialysine occurs exclusively at the amino moiety of the side chain. Remarkably, heterologous expression of C. elegans N-acetyltransferase D2023.4 in Escherichia coli, which does not possess a homologous gene, results in a pronounced resistance against the anti-metabolite thialysine. Furthermore, C. elegans N-acetyltransferase D2023.4 exhibits the highest homology with a number of GNATs found in numerous genomes from bacteria to mammals that have not been biochemically characterized so far, suggesting a novel group of GNAT enzymes closely related to spermidine/spermine-N1-acetyltransferase, but with a distinct substrate specificity. Taken together, we propose to name the enzyme ‘thialysine Nε-acetyltransferase’.

scholarly journals Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans

2016 ◽  
Vol 113 (36) ◽  
pp. 10055-10060 ◽  
Author(s):  
Xinxing Zhang ◽  
Kunhua Li ◽  
Rachel A. Jones ◽  
Steven D. Bruner ◽  
Rebecca A. Butcher
Keyword(s):  
Caenorhabditis Elegans ◽  
Nematode Species ◽  
Binding Pocket ◽  
Pheromone Biosynthesis ◽  
Atp Binding ◽  
Metabolic State ◽  
C Elegans ◽  
Acyl Coa Oxidase ◽  
Key Residues ◽  
And Behavior

Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state.

scholarly journals Activation of hatching in diapaused and quiescent Globodera pallida

Parasitology ◽  
2012 ◽  
Vol 140 (4) ◽  
pp. 445-454 ◽  
Author(s):  
JUAN E. PALOMARES-RIUS ◽  
JOHN T. JONES ◽  
PETER J. COCK ◽  
PABLO CASTILLO ◽  
VIVIAN C. BLOK
Keyword(s):  
Bursaphelenchus Xylophilus ◽  
Globodera Pallida ◽  
Parasitic Nematodes ◽  
Plant Parasitic Nematodes ◽  
Cyst Nematodes ◽  
Term Survival ◽  
C Elegans ◽  
Dauer Formation ◽  
Dorsal Gland

SUMMARYThe potato cyst nematodes (PCN) Globodera pallida and G. rostochiensis are major pests of potatoes. The G. pallida (and G. rostochiensis) life cycle includes both diapause and quiescent stages. Nematodes in dormancy (diapause or quiescent) are adapted for long-term survival and are more resistant to nematicides. This study analysed the mechanisms underlying diapause and quiescence. The effects of several compounds (8Br-cGMP, oxotremorine and atropine) on the activation of hatching were studied. The measurements of some morphometric parameters in diapaused and quiescent eggs after exposure to PRD revealed differences in dorsal gland length, subventral gland length and dorsal gland nucleolus. In addition, the expression of 2 effectors (IVg9 and cellulase) was not induced in diapaused eggs in water or PRD, while expression was slightly induced in quiescent eggs. Finally, we performed a comparative study to identify orthologues of C. elegans diapause related genes in plant-parasitic nematodes (G. pallida, Meloidogyne incognita, M. hapla and Bursaphelenchus xylophilus). This analysis suggested that it was not possible to identify G. pallida orthologues of the majority of C. elegans genes involved in the control of dauer formation. All these data suggest that G. pallida may use different mechanisms to C. elegans in regulating the survival stage.

scholarly journals Transcriptome dynamics predict thermotolerance in Caenorhabditis elegans

2019 ◽  
Author(s):  
Katharina Jovic ◽  
Jacopo Grilli ◽  
Mark G. Sterken ◽  
Basten L. Snoek ◽  
Joost A. G. Riksen ◽  
...  
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Intrinsic Property ◽  
Recovery Process ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome

AbstractBackgroundThe detrimental effects of a short bout of stress can persist, and potentially turn lethal, long after the return to normal conditions. Thermotolerance, which is the capacity of an organism to withstand relatively extreme temperatures, is influenced by the response during stress exposure, as well as the recovery process afterwards. While heat-shock response mechanisms have been studied intensively, predicting thermal tolerance remains a challenge.ResultsHere, we use the nematode Caenorhabditis elegans to measure transcriptional resilience to heat stress and predict thermotolerance. Using high dimensionality reduction techniques in combination with genome-wide gene expression profiles collected in three high resolution time-series during control, heat stress and recovery conditions, we infer a quantitative scale capturing the extent of stress-induced transcriptome dynamics in a single value. This scale provides a basis for evaluating transcriptome resilience, defined here as the ability to depart from stress-expression dynamics during recovery. Independent replication across multiple highly divergent genotypes reveals that the transcriptional resilience parameter measured after a spike in temperature is quantitatively linked to long-term survival after heat stress.ConclusionOur findings imply that thermotolerance is an intrinsic property that pre-determines long term outcome of stress and can be predicted by the transcriptional resilience parameter. Inferring the transcriptional resilience parameters of higher organisms could aid in evaluating rehabilitation strategies after stresses such as disease and trauma.

Caenorhabditis elegans Learning and Memory

2019 ◽  
Author(s):  
James S.H. Wong ◽  
Catharine H. Rankin
Keyword(s):  
Carbon Dioxide ◽  
Caenorhabditis Elegans ◽  
Classical Conditioning ◽  
Learning And Memory ◽  
Long Term Memory ◽  
Context Conditioning ◽  
Term Memory ◽  
C Elegans

The nematode, Caenorhabditis elegans (C. elegans), is an organism useful for the study of learning and memory at the molecular, cellular, neural circuitry, and behavioral levels. Its genetic tractability, transparency, connectome, and accessibility for in vivo cellular and molecular analyses are a few of the characteristics that make the organism such a powerful system for investigating mechanisms of learning and memory. It is able to learn and remember across many sensory modalities, including mechanosensation, chemosensation, thermosensation, oxygen sensing, and carbon dioxide sensing. C. elegans habituates to mechanosensory stimuli, and shows short-, intermediate-, and long-term memory, and context conditioning for mechanosensory habituation. The organism also displays chemotaxis to various chemicals, such as diacetyl and sodium chloride. This behavior is associated with several forms of learning, including state-dependent learning, classical conditioning, and aversive learning. C. elegans also shows thermotactic learning in which it learns to associate a particular temperature with the presence or absence of food. In addition, both oxygen preference and carbon dioxide avoidance in C. elegans can be altered by experience, indicating that they have memory for the oxygen or carbon dioxide environment they were reared in. Many of the genes found to underlie learning and memory in C. elegans are homologous to genes involved in learning and memory in mammals; two examples are crh-1, which is the C. elegans homolog of the cAMP response element-binding protein (CREB), and glr-1, which encodes an AMPA glutamate receptor subunit. Both of these genes are involved in long-term memory for tap habituation, context conditioning in tap habituation, and chemosensory classical conditioning. C. elegans offers the advantage of having a very small nervous system (302 neurons), thus it is possible to understand what these conserved genes are doing at the level of single identified neurons. As many mechanisms of learning and memory in C. elegans appear to be similar in more complex organisms including humans, research with C. elegans aids our ever-growing understanding of the fundamental mechanisms of learning and memory across the animal kingdom.

Long-term sediment exposure to ZnO nanoparticles induces oxidative stress in Caenorhabditis elegans

2019 ◽  
Vol 6 (8) ◽  
pp. 2602-2614 ◽  
Author(s):  
Chi-Wei Huang ◽  
Shang-Wei Li ◽  
Vivian Hsiu-Chuan Liao
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Zno Nanoparticles ◽  
Gene Activation ◽  
Benthic Organism ◽  
Zno Nps ◽  
C Elegans ◽  
Sediment Exposure

Long-term sediment exposure to ZnO-NPs induces oxidative stress in benthic organism C. elegans which is mediated by the transcription factor DAF-16/FOXO triggering stress-responsive gene activation.

scholarly journals Embryonic Methamphetamine Exposure Inhibits Methamphetamine Cue Conditioning and Reduces Dopamine Concentrations in Adult N2 Caenorhabditis elegans

2016 ◽  
Vol 38 (2) ◽  
pp. 139-149 ◽  
Author(s):  
Simon N. Katner ◽  
Bethany S. Neal-Beliveau ◽  
Eric A. Engleman
Keyword(s):  
Caenorhabditis Elegans ◽  
Chloride Ions ◽  
Well Test ◽  
Long Term Effects ◽  
Liquid Filtration ◽  
C Elegans ◽  
Embryonic Exposure ◽  
Conditioning Data ◽  
Food Conditioning

Methamphetamine (MAP) addiction is substantially prevalent in today's society, resulting in thousands of deaths and costing billions of dollars annually. Despite the potential deleterious consequences, few studies have examined the long-term effects of embryonic MAP exposure. Using the invertebrate nematode Caenorhabditis elegans allows for a controlled analysis of behavioral and neurochemical changes due to early developmental drug exposure. The objective of the current study was to determine the long-term behavioral and neurochemical effects of embryonic exposure to MAP in C. elegans. In addition, we sought to improve our conditioning and testing procedures by utilizing liquid filtration, as opposed to agar, and smaller, 6-well testing plates to increase throughput. Wild-type N2 C. elegans were embryonically exposed to 50 μM MAP. Using classical conditioning, adult-stage C. elegans were conditioned to MAP (17 and 500 μM) in the presence of either sodium ions (Na+) or chloride ions (Cl-) as conditioned stimuli (CS+/CS-). Following conditioning, a preference test was performed by placing worms in 6-well test plates spotted with the CS+ and CS- at opposite ends of each well. A preference index was determined by counting the number of worms in the CS+ target zone divided by the total number of worms in the CS+ and CS- target zones. A food conditioning experiment was also performed in order to determine whether embryonic MAP exposure affected food conditioning behavior. For the neurochemical experiments, adult worms that were embryonically exposed to MAP were analyzed for dopamine (DA) content using high-performance liquid chromatography. The liquid filtration conditioning procedure employed here in combination with the use of 6-well test plates significantly decreased the time required to perform these experiments and ultimately increased throughput. The MAP conditioning data found that pairing an ion with MAP at 17 or 500 μM significantly increased the preference for that ion (CS+) in worms that were not pre-exposed to MAP. However, worms embryonically exposed to MAP did not exhibit significant drug cue conditioning. The inability of MAP-exposed worms to condition to MAP was not associated with deficits in food conditioning, as MAP-exposed worms exhibited a significant cue preference associated with food. Furthermore, our results found that embryonic MAP exposure reduced DA levels in adult C. elegans, which could be a key mechanism contributing to the long-term effects of embryonic MAP exposure. It is possible that embryonic MAP exposure may be impairing the ability of C. elegans to learn associations between MAP and the CS+ or inhibiting the reinforcing properties of MAP. However, our food conditioning data suggest that MAP-exposed animals can form associations between cues and food. The depletion of DA levels during embryonic exposure to MAP could be responsible for driving either of these processes during adulthood.

scholarly journals Transcriptome resilience predicts thermotolerance in Caenorhabditis elegans

BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Katharina Jovic ◽  
Jacopo Grilli ◽  
Mark G. Sterken ◽  
Basten L. Snoek ◽  
Joost A. G. Riksen ◽  
...  
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Principal Component ◽  
Intrinsic Property ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome

Abstract Background The detrimental effects of a short bout of stress can persist and potentially turn lethal, long after the return to normal conditions. Thermotolerance, which is the capacity of an organism to withstand relatively extreme temperatures, is influenced by the response during stress exposure, as well as the recovery process afterwards. While heat-shock response mechanisms have been studied intensively, predicting thermal tolerance remains a challenge. Results Here, we use the nematode Caenorhabditis elegans to measure transcriptional resilience to heat stress and predict thermotolerance. Using principal component analysis in combination with genome-wide gene expression profiles collected in three high-resolution time series during control, heat stress, and recovery conditions, we infer a quantitative scale capturing the extent of stress-induced transcriptome dynamics in a single value. This scale provides a basis for evaluating transcriptome resilience, defined here as the ability to depart from stress-expression dynamics during recovery. Independent replication across multiple highly divergent genotypes reveals that the transcriptional resilience parameter measured after a spike in temperature is quantitatively linked to long-term survival after heat stress. Conclusion Our findings imply that thermotolerance is an intrinsic property that pre-determines long-term outcome of stress and can be predicted by the transcriptional resilience parameter. Inferring the transcriptional resilience parameters of higher organisms could aid in evaluating rehabilitation strategies after stresses such as disease and trauma.

scholarly journals Ancestral function of Inhibitors-of-kappaB regulates Caenorhabditis elegans development

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
David Brena ◽  
Joan Bertran ◽  
Montserrat Porta-de-la-Riva ◽  
Yolanda Guillén ◽  
Eric Cornes ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Histone Demethylase ◽  
Specific Gene ◽  
Main Function ◽  
Negative Regulators ◽  
Developmental Defects ◽  
C Elegans ◽  
Polycomb Proteins ◽  
Ancestral Function

Abstract Mammalian IκB proteins (IκBs) exert their main function as negative regulators of NF-κB, a central signaling pathway controlling immunity and inflammation. An alternative chromatin role for IκBs has been shown to affect stemness and cell differentiation. However, the involvement of NF-κB in this function has not been excluded. NFKI-1 and IKB-1 are IκB homologs in Caenorhabditis elegans, which lacks NF-κB nuclear effectors. We found that nfki-1 and ikb-1 mutants display developmental defects that phenocopy mutations in Polycomb and UTX-1 histone demethylase, suggesting a role for C. elegans IκBs in chromatin regulation. Further supporting this possibility (1) we detected NFKI-1 in the nucleus of cells; (2) NFKI-1 and IKB-1 bind to histones and Polycomb proteins, (3) and associate with chromatin in vivo, and (4) mutations in nfki-1 and ikb-1 alter chromatin marks. Based on these results, we propose that ancestral IκB inhibitors modulate Polycomb activity at specific gene subsets with an impact on development.

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