The C. elegans gene lin-36 acts cell autonomously in the lin-35 Rb pathway

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3449-3459 ◽  
Author(s):  
J.H. Thomas ◽  
H.R. Horvitz
Keyword(s):  
Amino Acids ◽  
Caenorhabditis Elegans ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Intercellular Signaling ◽  
Rb Protein ◽  
C Elegans ◽  
Rb Pathway ◽  
Vulval Precursor Cells ◽  
Novel Protein

The Caenorhabditis elegans gene lin-36 acts to antagonize Ras-mediated vulval induction in a pathway that includes genes with products similar to the mammalian retinoblastoma (Rb) protein and the Rb-binding protein p48. We report that lin-36 encodes a novel protein of 962 amino acids. We demonstrate that lin-36 functions in and is expressed in the vulval precursor cells, establishing that the lin-36 pathway is involved in intercellular signaling. We also report that the lin-36 pathway and/or another pathway that is functionally redundant with the lin-36 pathway antagonize a ligand-independent activity of the receptor tyrosine kinase/Ras vulval induction pathway.

scholarly journals sli-1, a negative regulator of let-23-mediated signaling in C. elegans.

Genetics ◽  
1995 ◽  
Vol 139 (4) ◽  
pp. 1553-1566 ◽  
Author(s):  
G D Jongeward ◽  
T R Clandinin ◽  
P W Sternberg
Keyword(s):  
Caenorhabditis Elegans ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Negative Regulator ◽  
Null Alleles ◽  
C Elegans ◽  
Severe Reduction ◽  
Abnormal Head ◽  
Hypomorphic Alleles ◽  
Different Tissues

Abstract By screening for suppressors of hypomorphic mutations of let-23, a receptor tyrosine kinase necessary for vulval induction in Caenorhabditis elegans, we recovered > or = 12 mutations defining the sli-1 (suppressor of lineage defect) locus. sli-1 mutations suppress four of five phenotypes associated with hypomorphic alleles of let-23 but do not suppress let-23 null alleles. Thus, a sli-1 mutation does not bypass the requirement for functional let-23 but rather allows more potent LET-23-dependent signaling. Mutations at the sli-1 locus are otherwise silent with respect to vulval differentiation and cause only a low-penetrance abnormal head phenotype. Mutations at sli-1 also suppress the vulval defects but not other defects associated with mutations of sem-5, whose product likely interacts with LET-23 protein during vulval induction. Mutations at sli-1 suppress lin-2, lin-7 and lin-10 mutations but only partially suppress lin-3 and let-60 mutations and do not suppress a lin-45 mutation. The sli-1 locus displays dosage sensitivity: severe reduction of function alleles of sli-1 are semidominant suppressors; a duplication of the sli-1(+) region enhances the vulvaless phenotype of hypomorphic mutations of let-23. We propose that sli-1 is a negative regulator that acts at or near the LET-23-mediated step of the vulval induction pathway. Our analysis suggests that let-23 can activate distinct signaling pathways in different tissues: one pathway is required for vulval induction; another pathway is involved in hermaphrodite fertility and is not regulated by sli-1.

scholarly journals An Evolutionarily Conserved Pathway Essential for Orsay Virus Infection of Caenorhabditis elegans

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Hongbing Jiang ◽  
Kevin Chen ◽  
Luis E. Sandoval ◽  
Christian Leung ◽  
David Wang
Keyword(s):  
Caenorhabditis Elegans ◽  
Virus Infection ◽  
Tyrosine Kinase ◽  
Model Organism ◽  
Wiskott Aldrich Syndrome ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Conserved Genes ◽  
Orsay Virus ◽  
Syndrome Protein

ABSTRACT Many fundamental biological discoveries have been made in Caenorhabditis elegans. The discovery of Orsay virus has enabled studies of host-virus interactions in this model organism. To identify host factors critical for Orsay virus infection, we designed a forward genetic screen that utilizes a virally induced green fluorescent protein (GFP) reporter. Following chemical mutagenesis, two Viro (virus induced reporter off) mutants that failed to express GFP were mapped to sid-3, a nonreceptor tyrosine kinase, and B0280.13 (renamed viro-2), an ortholog of human Wiskott-Aldrich syndrome protein (WASP). Both mutants yielded Orsay virus RNA levels comparable to that of the residual input virus, suggesting that they are not permissive for Orsay virus replication. In addition, we demonstrated that both genes affect an early prereplication stage of Orsay virus infection. Furthermore, it is known that the human ortholog of SID-3, activated CDC42-associated kinase (ACK1/TNK2), is capable of phosphorylating human WASP, suggesting that VIRO-2 may be a substrate for SID-3 in C. elegans. A targeted RNA interference (RNAi) knockdown screen further identified the C. elegans gene nck-1, which has a human ortholog that interacts with TNK2 and WASP, as required for Orsay virus infection. Thus, genetic screening in C. elegans identified critical roles in virus infection for evolutionarily conserved genes in a known human pathway. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection.

scholarly journals The Caenorhabditis elegans locus lin-15, a negative regulator of a tyrosine kinase signaling pathway, encodes two different proteins.

Genetics ◽  
1994 ◽  
Vol 137 (4) ◽  
pp. 987-997 ◽  
Author(s):  
S G Clark ◽  
X Lu ◽  
H R Horvitz
Keyword(s):  
Caenorhabditis Elegans ◽  
Tyrosine Kinase ◽  
Signaling Pathway ◽  
Genomic Region ◽  
Negative Regulator ◽  
Ras Signaling ◽  
Intercellular Signaling ◽  
Tyrosine Kinase Signaling ◽  
Genomic Regions ◽  
Mrna Precursor

Abstract The Caenorhabditis elegans locus lin-15 negatively regulates an intercellular signaling process that induces formation of the hermaphrodite vulva. The lin-15 locus controls two separate genetic activities. Mutants that lack both activities have multiple, ectopic pseudo-vulvae resulting from the overproduction of vulval cells, whereas mutants defective in only one lin-15 activity appear wild-type. lin-15 acts non-cell-autonomously to prevent the activation of a receptor tyrosine kinase/ras signaling pathway. We report here the molecular characterization of the lin-15 locus. The two lin-15 activities are encoded by contiguous genomic regions and by two distinct, non-overlapping transcripts that may be processed from a single mRNA precursor by trans-splicing. Based on the DNA sequence, the 719- and 1,440-amino acid lin-15 proteins are not similar to each other or to known proteins. lin-15 multivulva mutants, which are defective in both lin-15 activities, contain deletions and insertions that affect the lin-15 genomic region.

scholarly journals Multiple functions of let-23, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction.

Genetics ◽  
1991 ◽  
Vol 128 (2) ◽  
pp. 251-267 ◽  
Author(s):  
R V Aroian ◽  
P W Sternberg
Keyword(s):  
Caenorhabditis Elegans ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Egf Receptor ◽  
Kinase Gene ◽  
Multiple Functions ◽  
Tyrosine Kinase Gene ◽  
Receptor Tyrosine Kinase Gene ◽  
Epidermal Growth ◽  
Mutant Phenotypes

Abstract The let-23 gene, which encodes a putative tyrosine kinase of the epidermal growth factor (EGF) receptor subfamily, has multiple functions during Caenorhabditis elegans development. We show that let-23 function is required for vulval precursor cells (VPCs) to respond to the signal that induces vulval differentiation: a complete loss of let-23 function results in no induction. However, some let-23 mutations that genetically reduce but do not eliminate let-23 function result in VPCs apparently hypersensitive to inductive signal: as many as five of six VPCs can adopt vulval fates, in contrast to the three that normally do. These results suggest that the let-23 receptor tyrosine kinase controls two opposing pathways, one that stimulates vulval differentiation and another that negatively regulates vulval differentiation. Furthermore, analysis of 16 new let-23 mutations indicates that the let-23 kinase functions in at least five tissues. Since various let-23 mutant phenotypes can be obtained independently, the let-23 gene is likely to have tissue-specific functions.

Comparative developmental studies using Oscheius/Dolichorhabditis sp. CEW1 (Rhabditidae)

Nematology ◽  
2000 ◽  
Vol 2 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Marie Delattre ◽  
Marie-Laure Dichtel ◽  
Marie-Anne Félix
Keyword(s):  
Caenorhabditis Elegans ◽  
Genetic Analysis ◽  
Precursor Cells ◽  
Developmental Studies ◽  
Morphological Markers ◽  
Molecular Tools ◽  
Ras Gene ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
Anchor Cell

AbstractIn order to study the evolution of nematode vulva development, we focus on Oscheius/Dolichorhabditis sp. CEW1 (Rhabditidae) in comparison with Caenorhabditis elegans. In this species, the fates of the vulval precursor cells are determined by two successive nested inductions by the uterine anchor cell (instead of a single one in C. elegans). This hermaphroditic species can be cultured and handled like C. elegans. We review vulva development in this species. We present some molecular tools and the sequence of the Ras gene. This species is amenable to genetic analysis and we discuss the isolation of morphological markers. Afin d’étudier l’évolution du développement de la vulve des nématodes, nous nous concentrons sur l’espèce Oscheius/Dolichorhabditis sp. CEW1 (Rhabditidae) en la comparant à Caenorhabditis elegans. Dans cette espèce, les destinées des cellules précurseurs de la vulve sont déterminées par deux inductions emboîtées provenant de la cellule ancre de l’utérus (au lieu d’une seule chez C. elegans). Cette espèce hermaphrodite peut être élévée et manipulée comme C. elegans. Nous décrivons le développement de la vulve dans cette espèce. Nous présentons des outils moléculaires et la séquence du gène Ras. Les analyses génétiques sont possibles dans cette espèce et nous discutons l’isolement de marqueurs morphologiques.

The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury

2018 ◽  
Vol 11 (550) ◽  
pp. eaat0138
Author(s):  
Roman Vozdek ◽  
Yong Long ◽  
Dengke K. Ma
Keyword(s):  
Extracellular Matrix ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Large Scale ◽  
Hypoxia Inducible Factor ◽  
Metabolic Adaptation ◽  
Loss Of Function ◽  
Ecm Remodeling ◽  
C Elegans ◽  
Heme Peroxidases

Inadequate tissue oxygen, or hypoxia, is a central concept in the pathophysiology of ischemic disorders and cancer. Hypoxia promotes extracellular matrix (ECM) remodeling, cellular metabolic adaptation, and cancer cell metastasis. To discover new pathways through which cells respond to hypoxia, we performed a large-scale forward genetic screen inCaenorhabditis elegansand identified a previously uncharacterized receptor tyrosine kinase named HIR-1. Loss of function inhir-1phenocopied the impaired ECM integrity associated with hypoxia or deficiency in the oxygen-dependent dual oxidase, heme peroxidases, or cuticular collagens involved in ECM homeostasis. Genetic suppressor screens identified NHR-49 and MDT-15 as transcriptional regulators downstream of HIR-1. Furthermore,hir-1mutants showed defects in adapting to and recovering from prolonged severe hypoxia. We propose thatC. elegansHIR-1 coordinates hypoxia-inducible factor–independent responses to hypoxia and hypoxia-associated ECM remodeling through mechanisms that are likely conserved in other organisms.

Optimal levels of the essential amino acids histidine, lysine and threonine in Caenorhabditis elegans maintenance medium

Nematology ◽  
2008 ◽  
Vol 10 (4) ◽  
pp. 539-544 ◽  
Author(s):  
Nancy Lu ◽  
Xiaoyan Xiong
Keyword(s):  
Amino Acids ◽  
Caenorhabditis Elegans ◽  
Population Growth ◽  
Dry Weight ◽  
Essential Amino Acids ◽  
Maintenance Medium ◽  
C Elegans ◽  
Quantitative Studies ◽  
Free Living Nematode ◽  
Optimal Population

AbstractCurrent Caenorhabditis elegans Maintenance Medium (C-CeMM) is used to cultivate the free-living nematode, C. elegans. In C-CeMM, ten amino acids (AA) were found to be nutritionally essential. The optimal requirements of seven of these ten essential AA were determined previously. The objectives of the present study were to determine the optimal requirements of the remaining three essential AA: histidine, lysine and threonine. The Optimal Caenorhabditis elegans Maintenance Medium (O-CeMM) was formulated using the levels of all essential AA that supported the optimal population growth for C. elegans from previous quantitative studies and from the results obtained in the first part of this study. The efficacy of O-CeMM, C-CeMM, as well as Egg CeMM (E-CeMM), based on the essential AA ratio in hen's egg, was studied. The optimal requirements (mg ml–1) of histidine, lysine and threonine were determined to be 2.26 (8× C-CeMM), 1.03-2.06 (1× to 2× C-CeMM), and 0.717-2.86 (1× to 4× C-CeMM), respectively. It was found that O-CeMM supported a significantly higher (1.55 ∼ 1.60×) population growth (number of nematodes/ml) when compared with C-CeMM and E-CeMM. For both O-CeMM and C-CeMM, the AA efficiency ratio (AAER; g dry weight (wt) gain of C. elegans/g of total AA) was determined to be 0.18, which was significantly higher than the 0.15 that was determined in E-CeMM. Although the O-CeMM supported a significantly higher population growth, a higher level of histidine and consequently higher total AA were used in O-CeMM than in C-CeMM. Therefore, based on the findings on AAER, it was concluded that both the O-CeMM and C-CeMM were equally efficient for the cultivation of C. elegans.

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