aph-2 encodes a novel extracellular protein required for GLP-1-mediated signaling

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2481-2492
Author(s):  
C. Goutte ◽  
W. Hepler ◽  
K.M. Mickey ◽  
J.R. Priess
Keyword(s):  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Sequence Similarity ◽  
Cell Interactions ◽  
Extracellular Protein ◽  
Cell Surfaces ◽  
Transmembrane Receptors ◽  
Animal Development ◽  
C Elegans ◽  
Numerous Cell

In animal development, numerous cell-cell interactions are mediated by the GLP-1/LIN-12/NOTCH family of transmembrane receptors. These proteins function in a signaling pathway that appears to be conserved from nematodes to humans. We show here that the aph-2 gene is a new component of the GLP-1 signaling pathway in the early Caenorhabditis elegans embryo, and that proteins with sequence similarity to the APH-2 protein are found in Drosophila and vertebrates. During the GLP-1-mediated cell interactions in the C. elegans embryo, APH-2 is associated with the cell surfaces of both the signaling, and the responding, blastomeres. Analysis of chimeric embryos that are composed of aph-2(+) and aph-2(−) blastomeres suggests that aph-2(+) function may be provided by either the signaling or responding blastomere.

lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H)

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1373-1383 ◽  
Author(s):  
S. Christensen ◽  
V. Kodoyianni ◽  
M. Bosenberg ◽  
L. Friedman ◽  
J. Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Binding Sites ◽  
Feedback Loop ◽  
Target Genes ◽  
Sequence Similarity ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans ◽  
Downstream Target ◽  
Binding Factor ◽  
Flanking Regions

The homologous receptors LIN-12 and GLP-1 mediate diverse cell-signaling events during development of the nematode Caenorhabditis elegans. These two receptors appear to be functionally interchangeable and have sequence similarity to Drosophila Notch. Here we focus on a molecular analysis of the lag-1 gene (lin-12 -and glp-1), which plays a central role in LIN-12 and GLP-1-mediated signal transduction. We find that the predicted LAG-1 protein is homologous to two DNA-binding proteins: human C Promoter Binding Factor (CBF1) and Drosophila Suppressor of Hairless (Su(H)). Furthermore, we show that LAG-1 binds specifically to the DNA sequence RTGGGAA, previously identified as a CBF-1/Su(H)-binding site. Finally, we report that the 5′ flanking regions and first introns of the lin-12, glp-1 and lag-1 genes are enriched for potential LAG-1-binding sites. We propose that LAG-1 is a transcriptional regulator that serves as a primary link between the LIN-12 and GLP-1 receptors and downstream target genes in C. elegans. In addition, we propose that LAG-1 may be a key component of a positive feedback loop that amplifies activity of the LIN-12/GLP-1 pathway.

scholarly journals Lipopolysaccharide exposure induces oxidative damage in Caenorhabditis elegans: protective effects of carnosine

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Ma ◽  
Xiaoyuan Xu ◽  
Ranran Wang ◽  
Haijing Yan ◽  
Huijuan Yao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Protective Effects ◽  
Related Gene ◽  
Rt Pcr ◽  
C Elegans ◽  
Apoptosis Related Gene

Abstract Background The present study was designed to investigate the protective effects and mechanisms of carnosine on lipopolysaccharide (LPS)-induced injury in Caenorhabditis elegans. Methods C. elegans individuals were stimulated for 24 h with LPS (100 μg/mL), with or without carnosine (0.1, 1, 10 mM). The survival rates and behaviors were determined. The activities of superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) and levels of malondialdehyde (MDA) and glutathione (GSH) were determined using the respective kits. Reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the differential expression of sod-1, sod-2, sod-3, daf-16, ced-3, ced-9, sek-1, and pmk-1. Western blotting was used to determine the levels of SEK1, p38 mitogen-activated protein kinase (MAPK), cleaved caspase3, and Bcl-2. C. elegans sek-1 (km2) mutants and pmk-1 (km25) mutants were used to elucidate the role of the p38 MAPK signaling pathway. Results Carnosine improved the survival of LPS-treated C. elegans and rescued behavioral phenotypes. It also restrained oxidative stress by decreasing MDA levels and increasing SOD, GR, CAT, and GSH levels. RT-PCR results showed that carnosine treatment of wild-type C. elegans up-regulated the mRNA expression of the antioxidant-related genes sod-1, sod-2, sod-3, and daf-16. The expression of the anti-apoptosis-related gene ced-9 and apoptosis-related gene ced-3 was reversed by carnosine. In addition, carnosine treatment significantly decreased cleaved caspase3 levels and increased Bcl-2 levels in LPS-treated C. elegans. Apoptosis in the loss-of-function strains of the p38 MAPK signaling pathway was suppressed under LPS stress; however, the apoptotic effects of LPS were blocked in the sek-1 and pmk-1 mutants. The expression levels of sek-1 and pmk-1 mRNAs were up-regulated by LPS and reversed by carnosine. Finally, the expression of p-p38MAPK and SEK1 was significantly increased by LPS, which was reversed by carnosine. Conclusion Carnosine treatment protected against LPS injury by decreasing oxidative stress and inhibiting apoptosis through the p38 MAPK pathway.

scholarly journals A novel sphingolipid-TORC1 pathway critically promotes postembryonic development in Caenorhabditis elegans

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Huanhu Zhu ◽  
Huali Shen ◽  
Aileen K Sewell ◽  
Marina Kniazeva ◽  
Min Han
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Growth And Development ◽  
Postembryonic Development ◽  
Chain Fatty Acid ◽  
Metabolic Status ◽  
Animal Development ◽  
Branched Chain

Regulation of animal development in response to nutritional cues is an intensely studied problem related to disease and aging. While extensive studies indicated roles of the Target of Rapamycin (TOR) in sensing certain nutrients for controlling growth and metabolism, the roles of fatty acids and lipids in TOR-involved nutrient/food responses are obscure. Caenorhabditis elegans halts postembryonic growth and development shortly after hatching in response to monomethyl branched-chain fatty acid (mmBCFA) deficiency. Here, we report that an mmBCFA-derived sphingolipid, d17iso-glucosylceramide, is a critical metabolite in regulating growth and development. Further analysis indicated that this lipid function is mediated by TORC1 and antagonized by the NPRL-2/3 complex in the intestine. Strikingly, the essential lipid function is bypassed by activating TORC1 or inhibiting NPRL-2/3. Our findings uncover a novel lipid-TORC1 signaling pathway that coordinates nutrient and metabolic status with growth and development, advancing our understanding of the physiological roles of mmBCFAs, ceramides, and TOR.

scholarly journals Polyphenols from Blumea laciniata Extended the Lifespan and Enhanced Resistance to Stress in Caenorhabditis elegans via the Insulin Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1744
Author(s):  
Tao Chen ◽  
Siyuan Luo ◽  
Xiaoju Wang ◽  
Yiling Zhou ◽  
Yali Dai ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
Relevant Literature ◽  
Folk Medicine ◽  
Ageing Effect ◽  
C Elegans ◽  
Enhanced Resistance ◽  
Resistance To Stress

Blumea laciniata is widely used as a folk medicine in Asia, but relevant literature on it is rarely reported. We confirmed that polyphenol extract (containing chlorogenic acid, rutin, and luteolin-4-O-glucoside) from B. laciniata (EBL) showed strong antioxidant ability in vitro. Hence, in this work, we applied Caenorhabditis elegans to further investigate the antioxidant and anti-ageing abilities of EBL in vivo. The results showed that EBL enhanced the survival of C. elegans under thermal stress by 12.62% and sharply reduced the reactive oxygen species level as well as the content of malonaldehyde. Moreover, EBL increased the activities of antioxidant enzymes such as catalase and superoxide dismutase. Additionally, EBL promoted DAF-16, a transcription factor, into the nucleus. Besides, EBL extended the lifespan of C. elegans by 17.39%, showing an anti-ageing effect. Different mutants indicated that the insulin/IGF-1 signaling pathway participated in the antioxidant and anti-ageing effect of EBL on C. elegans.

scholarly journals An opioid-like system regulating feeding behavior in C. elegans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Mi Cheong Cheong ◽  
Alexander B Artyukhin ◽  
Young-Jai You ◽  
Leon Avery
Keyword(s):  
Caenorhabditis Elegans ◽  
Feeding Behavior ◽  
Opioid Receptors ◽  
Motor Neurons ◽  
Sequence Similarity ◽  
Rnai Screen ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
C Elegans ◽  
Opioid Neuropeptides

Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved worms, but not in worms lacking NPR-17, which encodes a protein with sequence similarity to opioid receptors. Opioid agonists activated heterologously expressed NPR-17, as did at least one NLP-24 peptide. Worms lacking the ASI neurons, which express npr-17, did not response to naloxone. Thus, we suggest that Caenorhabditis elegans has an endogenous opioid system that acts through NPR-17, and that opioids regulate feeding via ASI neurons. Together, these results suggest C. elegans may be the first genetically tractable invertebrate opioid model.

scholarly journals Insulin Receptor Substrate and p55 Orthologous Adaptor Proteins Function in theCaenorhabditis elegans daf-2/Insulin-like Signaling Pathway

2002 ◽  
Vol 277 (51) ◽  
pp. 49591-49597 ◽  
Author(s):  
Catherine A. Wolkow ◽  
Manuel J. Muñoz ◽  
Donald L. Riddle ◽  
Gary Ruvkun
Keyword(s):  
Insulin Receptor ◽  
Signaling Pathway ◽  
Sequence Similarity ◽  
Adaptor Proteins ◽  
Regulatory Subunit ◽  
Insulin Receptor Substrate ◽  
Genetic Screens ◽  
C Elegans ◽  
Insulin Receptor Substrates ◽  
Phosphoinositide 3 Kinase

An insulin-like signaling pathway regulates development and lifespan inCaenorhabditis elegans. Genetic screens that identified many components of theC. elegansinsulin pathway did not identify homologs of insulin receptor substrates or the phosphoinositide 3-kinase (PI3K) adaptor/regulatory subunit, which are both required for signaling by mammalian insulin/insulin-like growth factor I pathways. TheC. elegansgenome contains one homolog of each protein. TheC. elegansversions of insulin receptor substrate (IST-1) and PI3K p50/p55 (AAP-1) share moderate sequence similarity with their vertebrate andDrosophilacounterparts. Genetic experiments show thatist-1andaap-1potentiateC. elegansinsulin-like signaling, although they are not required for signaling in the pathway under most conditions. Worms lacking AAP-1 activity because of the mutationaap-1(m889) constitutively arrest development at the dauer larval stage when raised at high temperatures.aap-1mutants also live longer than wild-type animals, a phenotype observed in otherC. elegansmutants with defects in DAF-2 signaling. Interestingly, IST-1 appears to be required for signaling through a pathway that may act in parallel to AGE-1/PI3K.

scholarly journals Genetics of intercellular signalling in C. elegans

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 53-57
Author(s):  
Judith Austin ◽  
Eleanor M. Maine ◽  
Judith Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Molecular Level ◽  
Cell Interactions ◽  
Nematode Caenorhabditis Elegans ◽  
Developmental Potential ◽  
C Elegans ◽  
Intercellular Signalling ◽  
Mitotic Proliferation ◽  
Cell Cell

Cell–cell interactions play a significant role in controlling cell fate during development of the nematode Caenorhabditis elegans. It has been found that two genes, glp-1 and lin-12, are required for many of these decisions, glp-1 is required for induction of mitotic proliferation in the germline by the somatic distal tip cell and for induction of the anterior pharynx early in embryogenesis. lin-12 is required for the interactions between cells of equivalent developmental potential, which allow them to take on different fates. Comparison of these two genes on a molecular level indicates that they are similar in sequence and organization, suggesting that the mechanisms of these two different sets of cell–cell interactions are similar.

scholarly journals The Caenorhabditis elegans sel-1 Gene, a Negative Regulator of lin-12 and glp-1, Encodes a Predicted Extracellular Protein

Genetics ◽  
1996 ◽  
Vol 143 (1) ◽  
pp. 237-247 ◽  
Author(s):  
Barth Grant ◽  
Iva Greenwald
Keyword(s):  
Caenorhabditis Elegans ◽  
Genetic Interaction ◽  
Sequence Similarity ◽  
Extracellular Protein ◽  
Negative Regulator ◽  
Wild Type ◽  
Extragenic Suppressor ◽  
Null Phenotype

Abstract The Caenorhabditis elegans lin-12 and glp-1 genes encode members of the LIN-l2/NOTCH family of receptors. The sel-1 gene was identified as an extragenic suppressor of a lin-12 hypomorphic mutant. We show in this report that the sel-1 null phenotype is wild type, except for an apparent elevation in lin-12 and glp-1 activity in sensitized genetic backgrounds, and that this genetic interaction seems to be lin-12 and glp-1 specific. We also find that sel-1 encodes a predicted extracellular protein, with a domain sharing sequence similarity to predicted proteins from humans and yeast. SEL-1 may interact with the LIN-12 and GLP-1 receptors and/or their respective ligands to down-regulate signaling.

scholarly journals Deep Collection of Quantitative Nuclear Division Dynamics Data in RNAi-treated Caenorhabditis elegans Embryos

2020 ◽  
Author(s):  
Koji Kyoda ◽  
Hatsumi Okada ◽  
Hiroya Itoga ◽  
Shuichi Onami
Keyword(s):  
Statistical Analysis ◽  
Caenorhabditis Elegans ◽  
Clustering Analysis ◽  
Quantitative Data ◽  
Nuclear Division ◽  
List Type ◽  
Bioimage Informatics ◽  
Phenotypic Characters ◽  
Animal Development ◽  
C Elegans

SUMMARYRecent advances in bioimage informatics techniques have yielded quantitative data on multicellular dynamics from microscopy images of animal development. Several such data collections have been created for Caenorhabditis elegans embryos under various gene silencing conditions. However, because of the limited depth of the datasets, it is impractical to apply standard statistical methods to these collections. Here, we created a deep collection of quantitative data on nuclear division dynamics during the first three rounds of cell division in C. elegans embryos, in which 263 essential embryonic genes were silenced individually by RNA-mediated interference. The collection consists of datasets from 33 wild-type and 1142 RNAi-treated embryos, including five or more datasets for 189 genes. Application of a two-sample t-test identified 8660 reproducible RNAi-induced phenotypes for 421 phenotypic characters. Clustering analysis suggested 24 functional processes essential for early embryogenesis. Our collection is a rich resource for understanding animal development mechanisms.In BriefKyoda et al. used bioimage informatics techniques to create a deep collection of quantitative data on nuclear division dynamics in RNAi-treated C. elegans embryos for 263 essential embryonic genes. Statistical analysis identified 8660 reproducible RNAi phenotypes for 421 phenotypic characters. The collection is a rich resource for understanding animal development.HighlightsBioimage informatics quantified nuclear division dynamics in C. elegans embryosFrom RNAi-silenced embryos we collected 1142 data sets on 263 essential genesStatistical analysis identified 8660 reproducible RNAi phenotypesClustering analysis suggested 24 functional processes in C. elegans embryogenesis

Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic signalling activity of their extracellular domains in vivo

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4275-4282 ◽  
Author(s):  
K. Fitzgerald ◽  
I. Greenwald
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Cell Interactions ◽  
Regulatory Sequences ◽  
Cell Fate Decisions ◽  
C Elegans ◽  
Dsl Ligands ◽  
Mediate Cell ◽  
Intracellular Domains

Ligands of the Delta/Serrate/lag-2 (DSL) family and their receptors, members of the lin-12/Notch family, mediate cell-cell interactions that specify cell fate in invertebrates and vertebrates. In C. elegans, two DSL genes, lag-2 and apx-1, influence different cell fate decisions during development. Here we show that APX-1 can fully substitute for LAG-2 when expressed under the control of lag-2 regulatory sequences. In addition, we demonstrate that truncated forms lacking the transmembrane and intracellular domains of both LAG-2 and APX-1 can also substitute for endogenous lag-2 activity. Moreover, we provide evidence that these truncated forms are secreted and able to activate LIN-12 and GLP-1 ectopically. Finally, we show that expression of a secreted DSL domain alone may enhance endogenous LAG-2 signalling. Our data suggest ways that activated forms of DSL ligands in other systems may be created.

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