scholarly journals OAC-39 is an O-acyltransferase required for the synthesis of maradolipids in the dauer larva of C. elegans

2021 ◽  
Author(s):  
Sider Penkov
Keyword(s):  
Food Availability ◽  
Stress Resistance ◽  
Physiological Function ◽  
Polar Lipids ◽  
Intestinal Cells ◽  
Apical Region ◽  
Hyperosmotic Shock ◽  
C Elegans ◽  
Dauer Larva ◽  
Dauer Larvae

Upon overcrowding or low food availability, the nematode C. elegans enters a specialized diapause stage for survival, called the dauer larva. The growth-arrested, non-feeding dauer larva undergoes a profound metabolic and physiologic switch underlying its extraordinary stress resistance and longevity. One of the metabolic signatures of dauer larvae is the accumulation of the disaccharide trehalose, which lowers the sensitivity of worms to desiccation and hyperosmotic shock. Previously, we have found that trehalose is incorporated as a headgroup into dauer-specific 6,6′-di-O-acyltrehalose lipids, named maradolipids. Despite comprising a bulk fraction of the polar lipids in dauer larvae, little is known about the physiological function of maradolipds because the enzyme(s) involved in their synthesis has not yet been identified. Here, we report that the dauer-upregulated O-acyltransferase homolog OAC-39 is essential for the synthesis of maradolipids. This enzyme is enriched at the apical region of the intestinal cells of dauer larvae, where it might participate in the structuring of the gut lumen. As OAC-39 is most probably responsible for the last step of maradolipid synthesis, its identification will pave the way for the elucidation of the function of this obscure class of lipids.

Developmental arrest inCaenorhabditis elegansdauer larvae causes high expression of enzymes involved in thymidylate biosynthesis, similar to that found inTrichinellamuscle larvae

Parasitology ◽  
2005 ◽  
Vol 131 (2) ◽  
pp. 247-254 ◽  
Author(s):  
P. WIŃSKA ◽  
B. GOŁOS ◽  
J. CIEŚLA ◽  
Z. ZIELIŃSKI ◽  
T. FRĄCZYK ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thymidine Kinase ◽  
Thymidylate Synthase ◽  
Trichinella Spiralis ◽  
Recombinant Protein Expression ◽  
C Elegans ◽  
Protein Levels ◽  
Dauer Larva ◽  
Muscle Larvae ◽  
Dauer Larvae

Crude extract specific activities of thymidylate synthase, dUTPase, thymidine kinase and dihydrofolate reductase were high during the development ofCaenorhabditis elegans, the dauer larva activities being similar to those previously determined inTrichinella spiralisandT. pseudospiralismuscle larvae (with the exception of thymidine kinase, not detected inTrichinella). High thymidylate synthase expression in developmentally arrested larvae, demonstrated also at the mRNA and protein levels, is in agreement with a global cell cycle arrest of dauer larvae and indicates this unusual cell cycle regulation pattern can be shared by developmentally arrested larvae ofC. elegansand the twoTrichnellaspecies. Hence, the phenomenon may be characteristic for developmentally arrested larvae of different nematodes, rather than specific for the parasiticTrichinellamuscle larvae. EndogenousC. elegansthymidylate synthase was purified and its molecular properties compared with those of the recombinant protein, expression of the latter inE. colicells confirming the NCBI database sequence identity.

scholarly journals Opposing directions of stage-specific body length change in a close relative of C. elegans

2020 ◽  
Author(s):  
Eric W. Hammerschmith ◽  
Gavin C. Woodruff ◽  
Patrick C. Phillips
Keyword(s):  
Body Size ◽  
Body Length ◽  
Developmental Stages ◽  
Parasitic Nematodes ◽  
Close Relative ◽  
Evolutionary Divergence ◽  
Fig Wasp ◽  
C Elegans ◽  
Dauer Larva ◽  
Dauer Larvae

AbstractBackgroundBody size is a fundamental organismal trait. However, as body size and ecological contexts change across developmental time, evolutionary divergence may cause unexpected patterns of body size diversity among developmental stages. This may be particularly evident in polyphenic developmental stages specialized for dispersal. The dauer larva is such a stage in nematodes, and Caenorhabditis species disperse by traveling on invertebrate carriers. Here, we describe the morphology of the dispersal dauer larva of the nematode Caenorhabditis inopinata, whose adults can grow to be nearly twice as long as its close relative, the model organism C. elegans.ResultsWe find that the C. inopinata dauer larva is shorter and fatter than those of its close relatives C. elegans, C. briggsae, and C. tropicalis, despite its much longer adult stage. Additionally, many C. inopinata dauer larvae were ensheathed, an apparent novelty in this lineage reminiscent of the infective juveniles of parasitic nematodes. We also found abundant variation in dauer formation frequency among twenty-four wild isolates of C. inopinata, with many strains unable to produce dauer larvae under laboratory conditions.ConclusionMost Caenorhabditis species thrive on rotting plants and disperse on snails, slugs, or isopods (among others) whereas C. inopinata is ecologically divergent and thrives in fresh Ficus septica figs and disperses on their pollinating wasps. These wasps are at least an order of magnitude smaller in length than the vectors of other Caenorhabditis species. While there is some unknown factor of the fig environment that promotes elongated body size in C. inopinata adults, the smaller size of its fig wasp carrier may be driving the reduced body length of its dauer larva. Thus ecological divergence across multiple developmental stages can promote unexpected and opposing changes in body size within a single species.

scholarly journals Periodic ethanol supply as a path towards unlimited lifespan of C.elegans dauer larvae

2021 ◽  
Author(s):  
Xingyu Zhang ◽  
Sider Penkov ◽  
Teymuras V Kurzchalia ◽  
Vasily Zaburdeav
Keyword(s):  
Stress Resistance ◽  
Ethanol Concentration ◽  
Ethanol Metabolism ◽  
Feeding Frequency ◽  
Toxic Compounds ◽  
Dauer Larva ◽  
Stage Of Development ◽  
Metabolic Adaptations ◽  
Dauer Larvae ◽  
Harsh Conditions

The dauer larva is a specialized stage of development optimized for survival under harsh conditions that has been used as a model for stress resistance, metabolic adaptations, and longevity. Recent findings suggest that the dauer larva of C.elegans  may utilize external ethanol as an energy source to extend their lifespan. It was shown that while ethanol may serve as an effectively infinite source of energy, some toxic compounds accumulating as byproducts of its metabolism may lead to the damage of mitochondria and thus limit the lifespan of larvae. A minimal mathematical model was proposed to explain the connection between the lifespan of dauer larva and its ethanol metabolism. To explore theoretically if it is  possible to  extend even further the lifespan of dauer larvae, we incorporated two natural mechanisms describing the recovery of damaged mitochondria and elimination of toxic compounds, which were previously omitted in the model. Numerical simulations of the revised model suggest that while the ethanol concentration is constant, the lifespan still stays limited. However, if ethanol is supplied periodically, with a  suitable frequency and amplitude, the dauer could survive as long as we observe the system. Analytical methods further help to explain how the feeding frequency and amplitude affect the lifespan extension. Based on comparison of the model with experimental data for fixed ethanol concentration, we propose the range of feeding protocols that could lead to even longer dauer survival and can be tested experimentally.

Control of DAF-7 TGF-(alpha) expression and neuronal process development by a receptor tyrosine kinase KIN-8 in Caenorhabditis elegans

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5387-5398 ◽  
Author(s):  
M. Koga ◽  
M. Take-uchi ◽  
T. Tameishi ◽  
Y. Ohshima
Keyword(s):  
Tyrosine Kinases ◽  
Deletion Mutant ◽  
Process Development ◽  
Fusion Gene ◽  
Filling Defect ◽  
E Coli ◽  
C Elegans ◽  
Dauer Larva ◽  
Sensory Processes ◽  
Dauer Larvae

KIN-8 in C. elegans is highly homologous to human ROR-1 and 2 receptor tyrosine kinases of unknown functions. These kinases belong to a new subfamily related to the Trk subfamily. A kin-8 promoter::gfp fusion gene was expressed in ASI and many other neurons as well as in pharyngeal and head muscles. A kin-8 deletion mutant was isolated and showed constitutive dauer larva formation (Daf-c) phenotype: about half of the F(1) progeny became dauer larvae when they were cultivated on an old lawn of E. coli as food. Among the cells expressing kin-8::gfp, only ASI sensory neurons are known to express DAF-7 TGF-(beta), a key molecule preventing dauer larva formation. In the kin-8 deletion mutant, expression of daf-7::gfp in ASI was greatly reduced, dye-filling in ASI was specifically lost and ASI sensory processes did not completely extend into the amphid pore. The Daf-c phenotype was suppressed by daf-7 cDNA expression or a daf-3 null mutation. ASI-directed expression of kin-8 cDNA under the daf-7 promoter or expression by a heat shock promoter rescued the dye-filling defect, but not the Daf-c phenotype, of the kin-8 mutant. These results show that the kin-8 mutation causes the Daf-c phenotype through reduction of the daf-7 gene expression and that KIN-8 function is cell-autonomous for the dye-filling in ASI. KIN-8 is required for the process development of ASI, and also involved in promotion of daf-7 expression through a physiological or developmental function.

scholarly journals UHPLC-IM-Q-ToFMS analysis of maradolipids, found exclusively in Caenorhabditis elegans dauer larvae

2021 ◽  
Vol 413 (8) ◽  
pp. 2091-2102
Author(s):  
Michael Witting ◽  
Ulrike Schmidt ◽  
Hans-Joachim Knölker
Keyword(s):  
Caenorhabditis Elegans ◽  
Developmental Stage ◽  
Ion Mobility ◽  
Environmental Conditions ◽  
Multidimensional Data ◽  
Specific Class ◽  
Lipid Profiling ◽  
C Elegans ◽  
Tandem Mass Spectrometric ◽  
Dauer Larvae

AbstractLipid identification is one of the current bottlenecks in lipidomics and lipid profiling, especially for novel lipid classes, and requires multidimensional data for correct annotation. We used the combination of chromatographic and ion mobility separation together with data-independent acquisition (DIA) of tandem mass spectrometric data for the analysis of lipids in the biomedical model organism Caenorhabditis elegans. C. elegans reacts to harsh environmental conditions by interrupting its normal life cycle and entering an alternative developmental stage called dauer stage. Dauer larvae show distinct changes in metabolism and morphology to survive unfavorable environmental conditions and are able to survive for a long time without feeding. Only at this developmental stage, dauer larvae produce a specific class of glycolipids called maradolipids. We performed an analysis of maradolipids using ultrahigh performance liquid chromatography-ion mobility spectrometry-quadrupole-time of flight-mass spectrometry (UHPLC-IM-Q-ToFMS) using drift tube ion mobility to showcase how the integration of retention times, collisional cross sections, and DIA fragmentation data can be used for lipid identification. The obtained results show that combination of UHPLC and IM separation together with DIA represents a valuable tool for initial lipid identification. Using this analytical tool, a total of 45 marado- and lysomaradolipids have been putatively identified and 10 confirmed by authentic standards directly from C. elegans dauer larvae lipid extracts without the further need for further purification of glycolipids. Furthermore, we putatively identified two isomers of a lysomaradolipid not known so far. Graphical abstract

Streblus asper Lour. exerts MAPK and SKN-1 mediated anti-aging, anti-photoaging activities and imparts neuroprotection by ameliorating Aβ in Caenorhabditis elegans

2021 ◽  
pp. 1-17
Author(s):  
Mani Iyer Prasanth ◽  
James Michael Brimson ◽  
Dicson Sheeja Malar ◽  
Anchalee Prasansuklab ◽  
Tewin Tencomnao
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Vital Role ◽  
Transgenic Strain ◽  
Wild Type ◽  
Neuroprotective Effects ◽  
C Elegans ◽  
Streblus Asper

BACKGROUND: Streblus asper Lour., has been reported to have anti-aging and neuroprotective efficacies in vitro. OBJECTIVE: To analyze the anti-aging, anti-photoaging and neuroprotective efficacies of S. asper in Caenorhabditis elegans. METHODS: C. elegans (wild type and gene specific mutants) were treated with S. asper extract and analyzed for lifespan and other health benefits through physiological assays, fluorescence microscopy, qPCR and Western blot. RESULTS: The plant extract was found to increase the lifespan, reduce the accumulation of lipofuscin and modulate the expression of candidate genes. It could extend the lifespan of both daf-16 and daf-2 mutants whereas the pmk-1 mutant showed no effect. The activation of skn-1 was observed in skn-1::GFP transgenic strain and in qPCR expression. Further, the extract can extend the lifespan of UV-A exposed nematodes along with reducing ROS levels. Additionally, the extract also extends lifespan and reduces paralysis in Aβ transgenic strain, apart from reducing Aβ expression. CONCLUSIONS: S. asper was able to extend the lifespan and healthspan of C. elegans which was independent of DAF-16 pathway but dependent on SKN-1 and MAPK which could play a vital role in eliciting the anti-aging, anti-photoaging and neuroprotective effects, as the extract could impart oxidative stress resistance and neuroprotection.

scholarly journals Two Pleiotropic Classes of daf-2 Mutation Affect Larval Arrest, Adult Behavior, Reproduction and Longevity in Caenorhabditis elegans

Genetics ◽  
1998 ◽  
Vol 150 (1) ◽  
pp. 129-155 ◽  
Author(s):  
David Gems ◽  
Amy J Sutton ◽  
Mark L Sundermeyer ◽  
Patrice S Albert ◽  
Kevin V King ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Adult Longevity ◽  
Temperature Sensitive ◽  
Adult Behavior ◽  
Dauer Larva ◽  
Class 1 ◽  
Low Levels ◽  
Dauer Larvae ◽  
Overlapping Classes ◽  
Receptor Family

Abstract The nematode Caenorhabditis elegans responds to overcrowding and scarcity of food by arresting development as a dauer larva, a nonfeeding, long-lived, stress-resistant, alternative third-larval stage. Previous work has shown that mutations in the genes daf-2 (encoding a member of the insulin receptor family) and age-1 (encoding a PI 3-kinase) result in constitutive formation of dauer larvae (Daf-c), increased adult longevity (Age), and increased intrinsic thermotolerance (Itt). Some daf-2 mutants have additional developmental, behavioral, and reproductive defects. We have characterized in detail 15 temperature-sensitive and 1 nonconditional daf-2 allele to investigate the extent of daf-2 mutant defects and to examine whether specific mutant traits correlate with each other. The greatest longevity seen in daf-2 mutant adults was approximately three times that of wild type. The temperature-sensitive daf-2 mutants fell into two overlapping classes, including eight class 1 mutants, which are Daf-c, Age, and Itt, and exhibit low levels of L1 arrest at 25.5°. Seven class 2 mutants also exhibit the class 1 defects as well as some or all of the following: reduced adult motility, abnormal adult body and gonad morphology, high levels of embryonic and L1 arrest, production of progeny late in life, and reduced brood size. The strengths of the Daf-c, Age, and Itt phenotypes largely correlated with each other but not with the strength of class 2-specific defects. This suggests that the DAF-2 receptor is bifunctional. Examination of the null phenotype revealed a maternally rescued egg, L1 lethal component, and a nonconditional Daf-c component. With respect to the Daf-c phenotype, the dauer-defective (Daf-d) mutation daf-12(m20) was epistatic to daf-2 class 1 alleles but not the severe class 2 alleles tested. All daf-2 mutant defects were suppressed by the daf-d mutation daf-16(m26). Our findings suggest a new model for daf-2, age-1, daf-12, and daf-16 interactions.

Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress

2005 ◽  
Vol 288 (2) ◽  
pp. C467-C474 ◽  
Author(s):  
S. Todd Lamitina ◽  
Kevin Strange
Keyword(s):  
Insulin Signaling ◽  
Stress Resistance ◽  
Molecular Mechanisms ◽  
Organic Osmolytes ◽  
Dependent Manner ◽  
Animal Cells ◽  
Hypertonic Stress ◽  
C Elegans ◽  
Downstream Target ◽  
Molecular Damage

All cells adapt to hypertonic stress by regulating their volume after shrinkage, by accumulating organic osmolytes, and by activating mechanisms that protect against and repair hypertonicity-induced damage. In mammals and nematodes, inhibition of signaling from the DAF-2/IGF-1 insulin receptor activates the DAF-16/FOXO transcription factor, resulting in increased life span and resistance to some types of stress. We tested the hypothesis that inhibition of insulin signaling in Caenorhabditis elegans also increases hypertonic stress resistance. Genetic inhibition of DAF-2 or its downstream target, the AGE-1 phosphatidylinositol 3-kinase, confers striking resistance to a normally lethal hypertonic shock in a DAF-16-dependent manner. However, insulin signaling is not inhibited by or required for adaptation to hypertonic conditions. Microarray studies have identified 263 genes that are transcriptionally upregulated by DAF-16 activation. We identified 14 DAF-16-upregulated genes by RNA interference screening that are required for age- 1 hypertonic stress resistance. These genes encode heat shock proteins, proteins of unknown function, and trehalose synthesis enzymes. Trehalose levels were elevated approximately twofold in age- 1 mutants, but this increase was insufficient to prevent rapid hypertonic shrinkage. However, age- 1 animals unable to synthesize trehalose survive poorly under hypertonic conditions. We conclude that increased expression of proteins that protect eukaryotic cells against environmental stress and/or repair stress-induced molecular damage confers hypertonic stress resistance in C. elegans daf- 2/ age- 1 mutants. Elevated levels of solutes such as trehalose may also function in a cytoprotective manner. Our studies provide novel insights into stress resistance in animal cells and a foundation for new studies aimed at defining molecular mechanisms underlying these essential processes.

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