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Curr Top Microbiol Immunol,
2008]
Since Dr. Sidney Brenner first used it as an animal model system, the round worm Caenorhabditis elegans has significantly contributed to our understanding of important biological processes. Among them, the discovery in the 1990s of new gene silencing pathways orchestrated by tiny non-coding RNAs created a new field of research in biology. In this review, we will discuss the key players of the RNAi pathways in C. elegans and particularly the Argonaute genes, an impressive gene family of 27 members important in many aspects of these pathways.
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Bioessays,
2005]
Signal transduction pathways are largely conserved throughout the animal kingdom. The repertoire of pathways is limited and each pathway is used in different intercellular signaling events during the development of a given animal. For example, Wnt signaling is recruited, sometimes redundantly with other molecular pathways, in four cell specification events during Caenorhabditis elegans vulva development, including the activation of vulval differentiation. Strikingly,a recent study finds that Wnts act to repress vulval differentiation in the nematode Pristionchus pacificus,1 demonstrating evolutionary flexibility in the use of intercellular signaling pathways. BioEssays 27:765-769, 2005. (c) 2005 Wiley Periodicals, Inc.
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Trends Genet,
2004]
Collagens and proteins with collagen-like domains form large superfamilies in various species, and the numbers of known family members are increasing constantly. Vertebrates have at least 27 collagen types with 42 distinct polypeptide chains, >20 additional proteins with collagen-like domains and similar
to20 isoenzymes of various collagen-modifying enzymes. Caenorhabditis elegans has similar
to175 cuticle collagen polypeptides and two basement membrane collagens. Drosophila melanogaster has far fewer collagens than many other species but has similar
to20 polypeptides similar to the catalytic subunits of prolyl 4-hydroxylase, the key enzyme of collagen synthesis. More than 1300 mutations have so far been characterized in 23 of the 42 human collagen genes in various diseases, and many mouse models and C. elegans mutants are also available to analyse the collagen gene family and their modifying
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Chromosome Res,
2009]
The C. elegans dosage compensation complex (DCC) reduces transcript levels from each of the two hermaphrodite X chromosomes to equalize X-linked gene expression to that of XO males. Several of the proteins that comprise the DCC are homologous to subunits of the evolutionarily conserved condensin complexes, which in most organisms function in mitotic and meiotic chromosome condensation. These include the DCC subunits MIX-1 and DPY-27, which belong to the structural maintenance of chromosomes (SMC) family of proteins. Several of the C. elegans DCC subunits also perform double duty as members of the canonical meiotic and mitotic condensin complexes. Here, we review what is known about the C. elegans DCC and how study of this model might shed light on general mechanisms of domain-scale transcriptional regulation. We discuss how condensin-like complexes may be targeted to specific chromosomal locations for performance of their functions.
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Bioessays,
2005]
Cells become polarized to develop functional specializations and to distribute developmental determinants unequally during division. Studies that began in the nematode C. elegans have identified a group of largely conserved proteins, called PAR proteins, that play key roles in the polarization of many different cell types. During initial stages of cell polarization, certain PAR proteins become distributed asymmetrically along the cell cortex and subsequently direct the localization and/or activity of other proteins. Here I discuss recent findings on how PAR proteins become and remain asymmetric in three different contexts during C. elegans development: anterior-posterior polarization of the one-cell embryo, apicobasal polarization of non-epithelial early embryonic cells, and apicobasal polarization of epithelial cells. Although polarity within each of these cell types requires PAR proteins, the cues and regulators of PAR asymmetry can differ. BioEssays 27:126-135, 2005. (c) 2005 Wiley Periodicals, Inc.
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Bioessays,
2004]
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that bring about a diversity of fast synaptic actions. Analysis of the Caenorhabditis elegans genome has revealed one of the most-extensive and diverse nAChR gene families known, consisting of at least 27 subunits. Striking variation with possible functional implications has been observed in normally conserved motifs at the acetylcholine-binding site and in the channel-lining region. Some nAChR subunits are particular to neurons whilst others are present in both neurons and muscles. The localization of subunits in non-synaptic regions suggests novel roles for nAChRs. Genetic and heterologous expression studies have identified a subset of nAChR subunits that are important drug targets while the study of mutants has identified genes functionally-linked to nAChRs. Future studies using C. elegans offer the prospect of increasing our understanding of the functional diversity of a complex nAChR gene family as well as addressing the role of nAChRs and associated proteins in human disorders.
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Front Endocrinol (Lausanne),
2016]
Invertebrate models have generated many new insights into transmembrane signaling by cell-surface receptors. This review focuses on receptor guanylyl cyclases (rGCs) and describes recent advances in understanding their roles in sensory processing in the nematode, Caenorhabditis elegans. A complete analysis of the C. elegans genome elucidated 27 rGCs, an unusually large number compared with mammalian genomes, which encode 7 rGCs. Most C. elegans rGCs are expressed in sensory neurons and play roles in sensory processing, including gustation, thermosensation, olfaction, and phototransduction, among others. Recent studies have found that by producing a second messenger, guanosine 3',5'-cyclic monophosphate, some rGCs act as direct sensor molecules for ions and temperatures, while others relay signals from G protein-coupled receptors. Interestingly, genetic and biochemical analyses of rGCs provide the first example of an obligate heterodimeric rGC. Based on recent structural studies of rGCs in mammals and other organisms, molecular mechanisms underlying activation of rGCs are also discussed in this review.
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Bioessays,
2005]
This review explores the hypothesis that regulation of nucleocytoplasmic shuttling is a means of driving differentiation, using spermatogenesis as a model. The transition from undifferentiated spermatogonial stem cell to terminally differentiated spermatozoon is, at its most basic, a change in the repertoire of expressed genes. To effect this, the complement of nuclear proteins, such as transcription factors and chromatin remodelling components must change. Current knowledge of the nuclear proteins and nucleocytoplasmic transport machinery relevant to spermatogenesis is consolidated in this review, and their functional linkages are highlighted not only as a means of regulating nuclear protein composition, but also as a key mechanism regulating gene transcription and hence cell fate. Through this, we hypothesize that male germ cell differentiation is mediated through regulation of nuclear transport machinery components, and thereby of the access of critical factors to the nucleus. The importance of nucleocytoplasmic trafficking to male germ cell differentiation is discussed, using the sex-determining factors Sry and SOX9, cell cycle regulators, CREM and cofactors and the Smads as specific examples, together with the roles in gametogenesis for particular nuclear transport factors in Caenorhabditis elegans and Drosophila. BioEssays 27:1011-1025, 2005. (c) 2005 Wiley Periodicals, Inc.
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Ageing Res Rev,
2013]
Hormesis is the response of organisms to a mild stressor resulting in improved health and longevity. Mild heat shocks have been thought to induce hormetic response because they promote increased activity of heat shock proteins (HSPs), which may extend lifespan. Using data from 27 studies on 12 animal species, we performed a comparative meta-analysis to quantify the effect of heat shock exposure on longevity. Contrary to our expectations, heat shock did not measurably increase longevity in the overall meta-analysis, although we observed much heterogeneity among studies. Thus, we explored the relative contributions of different experimental variables (i.e. moderators). Higher temperatures, longer durations of heat shock exposure, increased shock repeat and less time between repeat shocks, all decreased the likelihood of a life-extending effect, as would be expected when a hormetic response crosses the threshold to being a damaging exposure. We conclude that there is limited evidence that mild heat stress is a universal way of promoting longevity at the whole-organism level. Life extension via heat-induced hormesis is likely to be constrained to a narrow parameter window of experimental conditions.
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Novartis Found Symp,
2002]
Genetics, genomics and electrophysiology are transforming our understanding of the nicotinic acetylcholine receptors (nAChRs). Caenorhabditis elegans contains the largest known family of nAChR subunit genes (27 members), while Drosophila melanogaster contains an exclusively neuronal nAChR gene family (10 members). In C. elegans, several genetic screens have enabled the identification of nAChR subunits, along with novel proteins that act upstream and downstream of functional nAChRs. The C. elegans genome project has identified many new candidate nAChR subunits and the calculated electrostatic potential energy profiles for the M2 channel-lining regions predict considerable functional diversity. The respective roles of subunits are under investigation using forward and reverse genetics. Electrophysiological and reporter genes studies have demonstrated roles for particular subunits in levamisole-sensitive muscle nAChRs and a role for nAChRs in pharyngeal pumping. Recombinant homomeric and heteromeric C. elegans nAChRs have been expressed in Xenopus laevis oocytes. In D. melanogaster, three new nAChR alpha subunits have been cloned, one of which shows multiple variant transcripts arising from alternative splicing and A-to-I pre-mRNA editing. Thus, studies on the genetic model organisms C. elegans and D. melanogaster have revealed different routes to generating molecular and functional diversity in the nAChR gene family and are providing new insights into the in vivo functions of individual family members.