Haemonchus contortus Transthyretin-Like Protein TTR-31 Plays Roles in Post-Embryonic Larval Development and Potentially Apoptosis of Germ Cells

Transthyretin (TTR)-like proteins play multi-function roles in nematode and are important component of excretory/secretory product in Haemonchus contortus. In this study, we functionally characterised a secretory transthyretin-like protein in the barber’s pole worm H. contortus. A full-length of transthyretin-like protein-coding gene (Hc-ttr-31) was identified in this parasitic nematode, representing a counterpart of Ce-ttr-31 in Caenorhabditis elegans. High transcriptional levels of Hc-ttr-31 were detected in the egg and early larval stages of H. contortus, with the lowest level measured in the adult stage, indicating a decreased transcriptional pattern of this gene during nematode development. Localisation analysis indicated a secretion of TTR-31 from the intestine to the gonad, suggesting additional roles of Hc-ttr-31 in nematode reproduction. Expression of Hc-ttr-31 and Ce-ttr-31 in C. elegans did not show marked influence on the nematode development and reproduction, whereas Hc-ttr-31 RNA interference-mediated gene knockdown of Ce-ttr-31 shortened the lifespan, decreased the brood size, slowed the pumping rate and inhibited the growth of treated worms. Particularly, gene knockdown of Hc-ttr-31 in C. elegans was linked to activated apoptosis signalling pathway, increased general reactive oxygen species (ROS) level, apoptotic germ cells and facultative vivipary phenotype, as well as suppressed germ cell removal signalling pathways. Taken together, Hc-ttr-31 appears to play roles in regulating post-embryonic larval development, and potentially in protecting gonad from oxidative stress and mediating engulfment of apoptotic germ cells. A better knowledge of these aspects should contribute to a better understanding of the developmental biology of H. contortus and a discovery of potential targets against this and related parasitic worms.

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Faculty Opinions recommendation of The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1020955.240571 ◽

2004 ◽

Author(s):

Michael Hall

Keyword(s):

Life Span ◽

Larval Development ◽

Signaling Pathway ◽

Insulin Signaling ◽

Insulin Signaling Pathway ◽

Tor Pathway ◽

C Elegans

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Faculty Opinions recommendation of C. elegans germ cells show temperature and age-dependent expression of Cer1, a Gypsy/Ty3-related retrotransposon.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717197869.792452870 ◽

2012 ◽

Author(s):

Andrew Chisholm

Keyword(s):

Germ Cells ◽

C Elegans ◽

Age Dependent

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glp-3 Is Required for Mitosis and Meiosis in the Caenorhabditis elegans Germ Line

Genetics ◽

10.1093/genetics/145.1.111 ◽

1997 ◽

Vol 145 (1) ◽

pp. 111-121 ◽

Cited By ~ 1

Author(s):

Lisa C Kadyk ◽

Eric J Lambie ◽

Judith Kimble

Keyword(s):

Caenorhabditis Elegans ◽

Germ Cells ◽

Germ Line ◽

Stem Cell Population ◽

Phenotypic Characterization ◽

Loss Of Function ◽

Dapi Staining ◽

Cell Cycles ◽

C Elegans ◽

Mitosis And Meiosis

The germ line is the only tissue in Caenorhabditis elegans in which a stem cell population continues to divide mitotically throughout life; hence the cell cycles of the germ line and the soma are regulated differently. Here we report the genetic and phenotypic characterization of the glp-3 gene. In animals homozygous for each of five recessive loss-of-function alleles, germ cells in both hermaphrodites and males fail to progress through mitosis and meiosis, but somatic cells appear to divide normally. Germ cells in animals grown at 15° appear by DAPI staining to be uniformly arrested at the G2/M transition with <20 germ cells per gonad on average, suggesting a checkpoint-mediated arrest. In contrast, germ cells in mutant animals grown at 25° frequently proliferate slowly during adulthood, eventually forming small germ lines with several hundred germ cells. Nevertheless, cells in these small germ lines never undergo meiosis. Double mutant analysis with mutations in other genes affecting germ cell proliferation supports the idea that glp-3 may encode a gene product that is required for the mitotic and meiotic cell cycles in the C. elegans germ line.

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The effects of flubendazole and its metabolites on the larval development of Haemonchus contortus (Nematoda: Trichostrongylidae): an in vitro study

Helminthologia ◽

10.2478/s11687-010-0042-7 ◽

2010 ◽

Vol 47 (4) ◽

pp. 269-272 ◽

Cited By ~ 6

Author(s):

H. Bártíková ◽

L. Skálová ◽

J. Lamka ◽

B. Szotáková ◽

M. Várady

Keyword(s):

Larval Development ◽

Haemonchus Contortus ◽

Anthelmintic Activity ◽

In Vitro Study ◽

Lethal Concentration ◽

Resistant Isolate ◽

Susceptible Isolate ◽

Marked Resistance ◽

Larval Development Test

AbstractThe anthelmintic effects of flubendazole (FLU), its two main metabolites reduced flubendazole (FLU-R) and hydrolyzed flubendazole (FLU-H), and thiabendazole (TBZ) were compared using an in vitro larval development test in two isolates of Haemonchus contortus, a fully susceptible isolate (HCS) and a multi-resistant isolate (HCR). Results were quantified as 50 % lethal concentration (LC50), 99 % lethal concentration (LC99), efficacy factor (EF), and resistance factor (RF). For HCS, both LC50 and LC99 of FLU were lower than those of the reference TBZ. The anthelmintic activity of FLU-R in HCS and HCR was 13 and 6 times lower than the activity of FLU, respectively. The anthelmintic activity of FLU-H was negligible (approximately 363–853 times lower) compared to that of FLU. Although a marked resistance of the HCR isolate to TBZ was confirmed, only a low tolerance to FLU-R and slightly higher tolerance to FLU were found.

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Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers

Parasitology ◽

10.1017/s0031182007000042 ◽

2007 ◽

Vol 134 (8) ◽

pp. 1111-1121 ◽

Cited By ~ 51

Author(s):

S. McCAVERA ◽

T. K. WALSH ◽

A. J. WOLSTENHOLME

Keyword(s):

Haemonchus Contortus ◽

Chloride Channels ◽

Macrocyclic Lactone ◽

Parasitic Nematodes ◽

C Elegans ◽

Molecular Tests ◽

Cooperia Oncophora ◽

Macrocyclic Lactone Resistance ◽

High Level ◽

Laboratory Models

SUMMARYLigand-gated chloride channels, including the glutamate-(GluCl) and GABA-gated channels, are the targets of the macrocyclic lactone (ML) family of anthelmintics. Changes in the sequence and expression of these channels can cause resistance to the ML in laboratory models, such as Caenorhabditis elegans and Drosophila melanogaster. Mutations in multiple GluCl subunit genes are required for high-level ML resistance in C. elegans, and this can be influenced by additional mutations in gap junction and amphid genes. Parasitic nematodes have a different complement of channel subunit genes from C. elegans, but a few genes, including avr-14, are widely present. A polymorphism in an avr-14 orthologue, which makes the subunit less sensitive to ivermectin and glutamate, has been identified in Cooperia oncophora, and polymorphisms in several subunits have been reported from resistant isolates of Haemonchus contortus. This has led to suggestions that ML resistance may be polygenic. Possible reasons for this, and its consequences for the development of molecular tests for resistance, are explored.

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Perinuclear P granules are the principal sites of mRNA export in adult C. elegans germ cells

Development ◽

10.1242/dev.044255 ◽

2010 ◽

Vol 137 (8) ◽

pp. 1305-1314 ◽

Cited By ~ 102

Author(s):

U. Sheth ◽

J. Pitt ◽

S. Dennis ◽

J. R. Priess

Keyword(s):

Germ Cells ◽

Mrna Export ◽

P Granules ◽

C Elegans

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Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline

Development ◽

10.1242/dev.126.5.1011 ◽

1999 ◽

Vol 126 (5) ◽

pp. 1011-1022 ◽

Cited By ~ 8

Author(s):

T.L. Gumienny ◽

E. Lambie ◽

E. Hartwieg ◽

H.R. Horvitz ◽

M.O. Hengartner

Keyword(s):

Cell Death ◽

Caenorhabditis Elegans ◽

Germ Cell ◽

Somatic Cell ◽

Cell Fate ◽

Germ Cells ◽

Mapk Pathway ◽

Apoptotic Cell ◽

C Elegans ◽

Pathway Activation

Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.

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DEPS-1 promotes P-granule assembly and RNA interference in C. elegans germ cells

Development ◽

10.1242/dev.015552 ◽

2008 ◽

Vol 135 (5) ◽

pp. 983-993 ◽

Cited By ~ 49

Author(s):

C. A. Spike ◽

J. Bader ◽

V. Reinke ◽

S. Strome

Keyword(s):

Rna Interference ◽

Germ Cells ◽

C Elegans

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Analysis of RNA associated with P granules in germ cells of C. elegans adults

Development ◽

10.1242/dev.128.8.1287 ◽

2001 ◽

Vol 128 (8) ◽

pp. 1287-1298 ◽

Cited By ~ 4

Author(s):

J.A. Schisa ◽

J.N. Pitt ◽

J.R. Priess

Keyword(s):

Germ Cells ◽

Rna Binding ◽

Nuclear Surface ◽

Binding Motifs ◽

P Granules ◽

C Elegans ◽

Specific Mrnas ◽

Tubulin Mrna ◽

Protein Components ◽

Cytoplasmic Structures

P granules are cytoplasmic structures of unknown function that are associated with germ nuclei in the C. elegans gonad, and are localized exclusively to germ cells, or germ cell precursors, throughout the life cycle. All the known protein components of P granules contain putative RNA-binding motifs, suggesting that RNA is involved in either the structure or function of the granules. However, no specific mRNAs have been identified within P granules in the gonad. We show here that P granules normally contain a low level of RNA, and describe conditions that increase this level. We present evidence that several, diverse mRNAs, including pos-1, mex-1, par-3, skn-1, nos-2 and gld-1 mRNA, are present at least transiently within P granules. In contrast, actin and tubulin mRNA and rRNA are either not present in P granules, or are present at relatively low levels. We show that pgl-1 and the glh (Vasa-related) gene family, which encode protein components of P granules, do not appear essential for RNA to concentrate in P granules; these proteins may instead function in events that are a prerequisite for RNAs to be transported efficiently from the nuclear surface.

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