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Nature Neuroscience,
2002]
A molecule that may be important for sorting presynaptic components into the developing axon is now revealed by a study using the genetic tools available in C. elegans.
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J Cell Mol Med,
2009]
Carbon dioxide (CO(2)) is an important gaseous molecule that maintains biosphere homeostasis and is an important cellular signalling molecule in all organisms. The transport of CO(2) through membranes has fundamental roles in most basic aspects of life in both plants and animals. There is a growing interest in understanding how CO(2) is transported into cells, how it is sensed by neurons and other cell types and in understanding the physiological and molecular consequences of elevated CO(2) levels (hypercapnia) at the cell and organism levels. Human pulmonary diseases and model organisms such as fungi, C. elegans, Drosophila and mice have been proven to be important in understanding of the mechanisms of CO(2) sensing and response.
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Matrix Biol,
1994]
Perlecan, the main proteoglycan of basement membranes and pericellular spaces, is one of the largest single-chain polypeptides of vertebrate animals. The five modules of perlecan are collated from protein building blocks evolutionarily related to molecules involved in nutrient metabolism, mitogenesis and adhesion. These structural motifs, when translated into multimeric functional units, could be effectively utilized by diverse tissues during development, remodelling or neoplastic growth. The protein is highly conserved across species and the available data indicate that this modular proteoglycan has evolved from ancient ancestors by gene duplication and exon shuffling. The discovery of a related molecule in the nematode C. elegans, and the development of skeletal muscle abnormalities in this animal when the perlecan-like molecule is truncated, opens new avenues of research.
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ACS Chem Biol,
2006]
Whereas the C. elegans genome was sequenced many years ago, the role of small molecule signals in its biology is still poorly understood. A recent publication reports the identification of two steroidal signaling molecules that regulate C. elegans reproductive development and dauer diapause via the nuclear receptor DAF-12. The two compounds, named dafachronic acids, represent the first endogenous ligands identified for any of the 284 nuclear receptors in C. elegans .
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Curr Protein Pept Sci,
2003]
ES-62 is a major secreted glycoprotein of the rodent filarial nematode Acanthocheilonema viteae and homologue of molecules found in filarial nematodes which parasitise humans. The molecule consists of a tetramer of apparently identical monomers of ~62 kDa which we have shown by sedimentation equilibrium analytical ultracentrifugation to strongly associate. ES-62 is one of several filarial nematode proteins to contain the unusual post-translational modification of phosphorylcholine (PC) addition. Specifically, we have found that PC is attached to one of three distinct N-type glycans we have characterised on the molecule. The amino acid sequence of ES-62 shows 37-39% identity with a family of 6 other proteins, some of which have been predicted to be amino- or carboxy-peptidases. We have also found that ES-62 is able to interact with a number of cells of the immune system, specifically B- and T-lymphocytes, macrophages and dendritic cells. Lymphocytes exposed to ES-62 in vitro or in vivo are less able to proliferate in response to ligation via the antigen receptor. Peritoneal macrophages pre-exposed to the molecule are less able to produce the cytokines IL-12, IL-6 and TNF-alpha following subsequent incubation with the classical stimulators IFNgamma and LPS. Dendritic cells allowed to mature in the presence of ES-62 acquire a phenotype, which allows them to induce anti-inflammatory "TH2-type" responses. With respect to immunomodulation, the PC moiety of the parasite molecule appears to be predominantly responsible for the effects on lymphocyte proliferation at least and we have also found that its removal converts the murine IgG antibody response to ES-62 from solely IgG1 to mixed IgG1/IgG2a. ES-62 appears to interact with cells of the immune system in a PC-dependent manner and, at least in part, via a molecule of ~82 kDa. Studies of the interaction in lymphocytes show that it is associated with activation of certain signal transduction molecules including a number of protein tyrosine kinases and mitogen activated protein kinases (MAPkinases). Although such activation is insufficient to induce proliferation, it serves to almost completely desensitise the cells to antigen-receptor ligation-induced activation of the phosphoinositide 3-kinase (PI-3-kinase) and Ras/MAPkinase pathways, events critical for lymphocyte proliferation. Such desensitisation reflects ES-62-primed recruitment of a number of negative regulators of these pathways, such as the phosphatases SHP-1 and Pac-1.
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Front Neuroanat,
2020]
The high synaptic density in the nervous system results from the ability of neurites to branch. Neuronal cell surface molecules play central roles during neurite branch formation. The underlying mechanisms of surface molecule activity have often been elucidated using invertebrates with simple nervous systems. Here, we review recent advances in understanding the molecular mechanisms of neurite branching in the nematode <i>Caenorhabditis elegans</i>. We discuss how cell surface receptor complexes link to and modulate actin dynamics to regulate dendritic and axonal branch formation. The mechanisms of neurite branching are often coupled with other neural circuit developmental processes, such as synapse formation and axon guidance, <i>via</i> the same cell-cell surface molecular interactions. We also cover ectopic and sex-specific neurite branching in <i>C. elegans</i> in an attempt to illustrate the importance of these studies in contributing to our understanding of conserved cell surface molecule regulation of neurite branch formation.
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Curr Opin Genet Dev,
1994]
Genetic studies have identified an extracellular path cue molecule, UNC-6, and a neuronal receptor, UNC-5, that act to guide migrating pioneer growth cones along the dorsoventral coordinate of the Caenorhabditis elegans body wall. Ectopic expression studies and characterization of mutants have demonstrated directly the instructive action of these molecules, suggesting a molecular model for how they perform their guidance functions. Recent evidence suggests that these and other genetically identified axon guidance molecules are likely to have vertebrate counterparts.
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Nat Cell Biol,
2003]
Cholesterol is a structural component of animal membranes that influences fluidity, permeability and formation of lipid microdomains. It is also a precursor to signalling molecules, including mammalian steroid hormones and insect ecdysones. The nematode Caenorhabditis elegans requires too little cholesterol for it to have a major role in membrane structure. Instead, its most probable signalling functions are to control molting and induce a specialized non-feeding larval stage, although no cholesterol-derived signalling molecule has yet been identified for these or any other functions.
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Curr Opin Neurobiol,
1996]
Neuronal growth cones respond to both contact-mediated and chemotropic guidance cues; these cues can be either attractive or repulsive. This past year has seen further characterization of two gene families implicated in long-range chemoattraction and chemorepulsion: the netrins and the semaphorins. Analysis of invertebrate members of these gene families demonstrates in vivo how netrins play multiple roles in axonal guidance in Caenorhabditis elegans, how specific domains of the netrin molecule confer attractive and repulsive guidance cues, and how semaphorins can function to generate neuromuscular specificity.
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Front Mol Neurosci,
2022]
Neuronal communication requires precise connectivity of neurite projections (axons and dendrites). Developing neurites express cell-surface receptors that interpret extracellular cues to enable correct guidance toward, and connection with, target cells. Spatiotemporal regulation of neurite guidance molecule expression by transcription factors (TFs) is critical for nervous system development and function. Here, we review how neurite development is regulated by TFs in the Caenorhabditis elegans nervous system. By collecting publicly available transcriptome and ChIP-sequencing data, we reveal gene expression dynamics during neurite development, providing insight into transcriptional mechanisms governing construction of the nervous system architecture.