Abstract:Starting with SAGE-libraries prepared from C. elegans FAC-sorted embryonic intestine cells (8E-16E cell stage), from total embryos and from purified oocytes, and taking advantage of the NextDB in situ hybridization data base, we define sets of genes highly expressed from the zygotic genome, and expressed either exclusively or preferentially in the embryonic intestine or in the intestine of newly hatched larvae; we had previously defined a similarly expressed set of genes from the adult intestine. We show that … Show more
“…Among the 1,122 genes identified as SMA-6 regulated (17), 144 of these overlapped with the B. pseudomallei infection response (Rf = 1.83). The GATA transcription factor ELT-2 is a positive regulator of intestinal immune responses (1,18). A significant enrichment (Rf = 8.43, hypergeometric probability P < 1 × 10 −6 ) was observed between ELT-2-regulated genes (19) and B. pseudomallei infection response genes, suggesting that ELT-2 might also contribute to the infection response of B. pseudomallei (Fig.…”
Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified ∼6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.innate immunity | ubiquitin-proteosomal system
“…Among the 1,122 genes identified as SMA-6 regulated (17), 144 of these overlapped with the B. pseudomallei infection response (Rf = 1.83). The GATA transcription factor ELT-2 is a positive regulator of intestinal immune responses (1,18). A significant enrichment (Rf = 8.43, hypergeometric probability P < 1 × 10 −6 ) was observed between ELT-2-regulated genes (19) and B. pseudomallei infection response genes, suggesting that ELT-2 might also contribute to the infection response of B. pseudomallei (Fig.…”
Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified ∼6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.innate immunity | ubiquitin-proteosomal system
“…While these findings establish the requirement for these two GATA factors, it is still unclear what role they serve in osmosensitive gene expression. Importantly, elt-2 and elt-3 appear to be generally required for expression of numerous genes in the intestine and hypodermis, respectively (31,51,(73)(74). Therefore, it is unclear whether either factor is induced by osmotic stress like NFAT5/TonEBP or whether they simply serve as tissue specifying cofactors for a yet to be identified osmotically inducible factor.…”
Section: R180 Salt and Water Homeostasis In C Elegansmentioning
Choe KP. Physiological and molecular mechanisms of salt and water homeostasis in the nematode Caenorhabditis elegans. Am J Physiol Regul Integr Comp Physiol 305: R175-R186, 2013. First published June 5, 2013 doi:10.1152/ajpregu.00109.2013.-Intracellular salt and water homeostasis is essential for all cellular life. Extracellular salt and water homeostasis is also important for multicellular organisms. Many fundamental mechanisms of compensation for osmotic perturbations are well defined and conserved. Alternatively, molecular mechanisms of detecting salt and water imbalances and regulating compensatory responses are generally poorly defined for animals. Throughout the last century, researchers studying vertebrates and vertebrate cells made critical contributions to our understanding of osmoregulation, especially mechanisms of salt and water transport and organic osmolyte accumulation. Researchers have more recently started using invertebrate model organisms with defined genomes and well-established methods of genetic manipulation to begin defining the genes and integrated regulatory networks that respond to osmotic stress. The nematode Caenorhabditis elegans is well suited to these studies. Here, I introduce osmoregulatory mechanisms in this model, discuss experimental advantages and limitations, and review important findings. Key discoveries include defining genetic mechanisms of osmolarity sensing in neurons, identifying protein damage as a sensor and principle determinant of hypertonic stress resistance, and identification of a putative sensor for hypertonic stress associated with the extracellular matrix. Many of these processes and pathways are conserved and, therefore, provide new insights into salt and water homeostasis in other animals, including mammals. osmoregulation; cell volume; ion; organic osmolyte; protein homeostasis; model organism SALT AND WATER HOMEOSTASIS is a fundamental requirement for metazoan life. Ion and water transport mechanisms that compensate for changes in composition and volume of intracellular and extracellular compartments have been generally well defined using vertebrate cell and in vivo models (38). Alternatively, the upstream molecular mechanisms that animal cells use to sense deviations in salt and water balance and regulate compensatory responses are still poorly characterized (20). Studies in brewer's yeast demonstrate that osmotic signal detection and transduction within a single eukaryotic cell can be highly complex with numerous components, acting in parallel pathways, that often cross-talk with other processes (40,55). Osmotic signal detection and transduction are likely to be even more complex in metazoans, which require homeostasis of both the extracellular and intracellular compartments and integration of responses between cells. Genetics is an extremely powerful approach for identifying and characterizing genes and proteins that function in complex biological processes but has been underutilized in the field of osmosensing and signal transduction in metazoans. In...
“…The C. elegans intestine is a ''simple'' epithelial tube consisting only of 20 polarized and tightly-associated cells which are, however, subject to multiple patterning and morphogenetic events [McGhee, 2007;McGhee et al, 2009]. We will show that intestinal morphogenesis and function can serve as examples of the interplay between IFs and other cytoskeletal filaments and their integration into a transcellular network by adherens-type cell-cell junctions.…”
Intermediate filaments (IFs) make up one of the three major fibrous cytoskeletal systems in metazoans. Numerous IF polypeptides are synthesized in cell typespecific combinations suggesting specialized functions. The review concentrates on IFs in the model organism Caenorhabditis elegans which carries great promise to elucidate the still unresolved mechanisms of IF assembly into complex networks and to determine IF function in a living organism. In contrast to Drosophila melanogaster, which lacks cytoplasmic IFs altogether, the nematode genome contains 11 genes coding for cytoplasmic IFs and only a single gene for a nuclear lamin. Its cytoplasmic IFs are expressed in developmentally and spatially defined patterns. As an example we present the case of the intestinal IFs which are abundant in the mechanically resilient endotube, a prominent feature of the C. elegans intestinal terminal web region. This IF-rich structure brings together all three cytoskeletal filaments that are integrated into a coherent entity by the C. elegans apical junction (CeAJ) thereby completely surrounding and stabilizing the intestinal lumen with its characteristic brush border. Concepts on the developmental establishment of the endotube in relation to polarization and its function for maintenance of epithelial integrity are discussed. Furthermore, possible connections of the cytoplasmic cytoskeleton to the nuclear lamin IFs and the importance of these links for nuclear positioning are summarized. Cell
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