The acyltransferase gene <i>bus‐1</i> exhibits conserved and specific expression in nematode rectal cells and reveals pathogen‐induced cell swelling

Gravato-Nobre, Maria J.; Hodgkin, Jonathan

doi:10.1002/dvdy.21792

Cited by 17 publications

(22 citation statements)

References 30 publications

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“…Activation of RHO-1* caused changes in cell morphology; cells appeared larger and were no longer organised around the rectal opening instead spreading towards the dorsal side of the animal (Figure 4 F, G, J and K). These changes were also observed in the rectal epithelial cells of wild-type animals infected with Microbacterium nematophilum (Figure 4F–I) [51]. Thus, RHO-1* acts cell-autonomously to alter rectal epithelial cell morphology in a manner similar to the innate immune response to pathogens.…”

Section: Resultsmentioning

confidence: 62%

Behavioral and Immune Responses to Infection Require Gαq- RhoA Signaling in C. elegans

2012

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Following pathogen infection the hosts' nervous and immune systems react with coordinated responses to the danger. A key question is how the neuronal and immune responses to pathogens are coordinated, are there common signaling pathways used by both responses? Using C. elegans we show that infection by pathogenic strains of M. nematophilum, but not exposure to avirulent strains, triggers behavioral and immune responses both of which require a conserved Gαq-RhoGEF Trio-Rho signaling pathway. Upon infection signaling by the Gαq pathway within cholinergic motorneurons is necessary and sufficient to increase release of the neurotransmitter acetylcholine and increase locomotion rates and these behavioral changes result in C. elegans leaving lawns of M. nematophilum. In the immune response to infection signaling by the Gαq pathway within rectal epithelial cells is necessary and sufficient to cause changes in cell morphology resulting in tail swelling that limits the infection. These Gαq mediated behavioral and immune responses to infection are separate, act in a cell autonomous fashion and activation of this pathway in the appropriate cells can trigger these responses in the absence of infection. Within the rectal epithelium the Gαq signaling pathway cooperates with a Ras signaling pathway to activate a Raf-ERK-MAPK pathway to trigger the cell morphology changes, whereas in motorneurons Gαq signaling triggers behavioral responses independent of Ras signaling. Thus, a conserved Gαq pathway cooperates with cell specific factors in the nervous and immune systems to produce appropriate responses to pathogen. Thus, our data suggests that ligands for Gq coupled receptors are likely to be part of the signals generated in response to M. nematophilum infection.

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Section: Resultsmentioning

confidence: 62%

Behavioral and Immune Responses to Infection Require Gαq- RhoA Signaling in C. elegans

2012

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“…For deformable, hydrophilic surfaces like those encountered on top of an agar gel, which is the usual place for examining C. elegans in a laboratory environment, it is not obvious how traction is exerted. As already noted in characterizing bus-8, bus-17, and bus-18 mutants ( Yook and Hodgkin 2007;Gravato-Nobre and Hodgkin 2008;Partridge et al 2008), several of the surfaceabnormal mutants identified by Bus phenotype also exhibit a ''Skiddy'' (Skd) locomotory mutant phenotype, in which the worm is able to generate a normal sinusoidal wave pattern but its body exhibits extensive slippage on agar and makes little forward progress. The three genes examined in detail in this work have only minor effects on this component of motility; bus-12 and bus-4 mutants exhibit a slight Skd phenotype, while bus-2 mutants move almost normally under normal laboratory conditions.…”

Section: Resultsmentioning

confidence: 76%

Glycosylation Genes Expressed in Seam Cells Determine Complex Surface Properties and Bacterial Adhesion to the Cuticle of Caenorhabditis elegans

et al. 2011

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The surface of the nematode Caenorhabditis elegans is poorly understood but critical for its interactions with the environment and with pathogens. We show here that six genes (bus-2, bus-4, and bus-12, together with the previously cloned srf-3, bus-8, and bus-17) encode proteins predicted to act in surface glycosylation, thereby affecting disease susceptibility, locomotory competence, and sexual recognition. Mutations in all six genes cause resistance to the bacterial pathogen Microbacterium nematophilum, and most of these mutations also affect bacterial adhesion and biofilm formation by Yersinia species, demonstrating that both infection and biofilm formation depend on interaction with complex surface carbohydrates. A new bacterial interaction, involving locomotory inhibition by a strain of Bacillus pumilus, reveals diversity in the surface properties of these mutants. Another biological property-contact recognition of hermaphrodites by males during mating-was also found to be impaired in mutants of all six genes. An important common feature is that all are expressed most strongly in seam cells, rather than in the main hypodermal syncytium, indicating that seam cells play the major role in secreting surface coat and consequently in determining environmental interactions. To test for possible redundancies in gene action, the 15 double mutants for this set of genes were constructed and examined, but no synthetic phenotypes were observed. Comparison of the six genes shows that each has distinctive properties, suggesting that they do not act in a linear pathway.

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“…bus-8 mutations cause cuticle defects that allow multiple drugs to invade the worm cuticle. We chose the bus-8 allele e2698 because it has high cuticle permeability to diverse small molecules and lectins (6), yet the animals are grossly phenotypically normal (7). We confirmed that motor function in the bus-8(e2698) animals is similar to wild type using a standard liquid thrashing assay (Figure S1), and that bus-8(e2698) has increased sensitivity to several different toxic compounds (Figure S2).…”

Section: Resultsmentioning

confidence: 99%

Dopamine D2 Receptor Antagonism Suppresses Tau Aggregation and Neurotoxicity

McCormick

Wheeler

Guthrie

et al. 2013

Biological Psychiatry

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Background Tauopathies, including Alzheimer’s disease (AD) and frontotemporal dementia, are diseases characterized by the formation of pathological tau protein aggregates in the brain and progressive neurodegeneration. Presently no effective disease modifying treatments exist for tauopathies. Methods To identify drugs targeting tau neurotoxicity, we have used a C. elegans model of tauopathy to screen a drug library containing 1120 compounds approved for human use for the ability to suppress tau-induced behavioral effects. Results One compound, the typical antipsychotic azaperone, improved the motility of tau transgenic worms, reduced levels of insoluble tau, and was protective against neurodegeneration. We found that azaperone reduces insoluble tau in a human cell culture model of tau aggregation, and that other antipsychotic drugs (flupenthixol, perphenazine, and zotepine) also ameliorate the effects of tau expression in both models. Conclusions Reduction of dopamine signaling through the dopamine D2 receptor with the use of gene knockouts in C. elegans or RNAi knockdown in human cell culture have similar protective effects against tau toxicity. These results suggest dopamine D2 receptor antagonism holds promise as a potential neuroprotective strategy for targeting tau aggregation and neurotoxicity.

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The acyltransferase gene bus‐1 exhibits conserved and specific expression in nematode rectal cells and reveals pathogen‐induced cell swelling

Cited by 17 publications

References 30 publications

Behavioral and Immune Responses to Infection Require Gαq- RhoA Signaling in C. elegans

Behavioral and Immune Responses to Infection Require Gαq- RhoA Signaling in C. elegans

Glycosylation Genes Expressed in Seam Cells Determine Complex Surface Properties and Bacterial Adhesion to the Cuticle of Caenorhabditis elegans

Dopamine D2 Receptor Antagonism Suppresses Tau Aggregation and Neurotoxicity

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