-
[
Dev Cell,
2004]
The C. elegans sex-determining gene
tra-2 is subject to multiple forms of regulation. A report in the June 4 issue of Molecular Cell now shows that proteins associated with the
tra-2 mRNA determine its pathway of nuclear export and influence its cytoplasmic fate. These findings demonstrate an additional level of control and link nuclear export to the regulation of sexual development.
-
[
Biochem Soc Trans,
2016]
Phosphatidylinositol (PI) is the precursor lipid for the synthesis of PI 4,5-bisphosphate [PI(4,5)P2] at the plasma membrane (PM) and is sequentially phosphorylated by the lipid kinases, PI 4-kinase and phosphatidylinositol 4-phosphate (PI4P)-5-kinase. Receptor-mediated hydrolysis of PI(4,5)P2 takes place at the PM but PI resynthesis occurs at the endoplasmic reticulum (ER). Thus PI(4,5)P2 resynthesis requires the reciprocal transport of two key intermediates, phosphatidic acid (PA) and PI between the ER and the PM. PI transfer proteins (PITPs), defined by the presence of the PITP domain, can facilitate lipid transfer between membranes; the PITP domain comprises a hydrophobic cavity with dual specificity but accommodates a single phospholipid molecule. The class II PITP, retinal degeneration typeB (RdgB) is a multi-domain protein and its PITP domain can bind and transfer PI and PA. In Drosophila photoreceptors, a well-defined G-protein-coupled phospholipase C (PLC) signalling pathway, phototransduction defects resulting from loss of RdgB can be rescued by expression of the PITP domain provided it is competent for both PI and PA transfer. We propose that RdgB proteins maintain PI(4,5)P2 homoeostasis after PLC activation by facilitating the reciprocal transport of PA and PI at ER-PM membrane contact sites.
-
[
Sci STKE,
2000]
Adenosine diphosphate-ribosylation factor (Arf) proteins are members of the Arf arm of the Ras superfamily of guanosine triphosphate (GTP)-binding proteins. Arfs are named for their activity as cofactors for cholera toxin-catalyzed adenosine diphosphate-ribosylation of the heterotrimeric G protein Gs. Physiologically, Arfs regulate membrane traffic and the actin cytoskeleton. Arfs function both constitutively within the secretory pathway and as targets of signal transduction in the cell periphery. In each case, the controlled binding and hydrolysis of GTP is critical to Arf function. The activities of some guanine nucleotide exchange factors (GEFs) and guanosine triphosphatase (GTPase)-activating proteins (GAPs) are stimulated by phosphoinositides, including phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidic acid (PA), likely providing both a means to respond to regulatory signals and a mechanism to coordinate GTP binding and hydrolysis. Arfs affect membrane traffic in part by recruiting coat proteins, including COPI and clathrin adaptor complexes, to membranes. However, Arf function likely involves many additional biochemical activities. Arf activates phospholipase D and phosphatidylinositol 4-phosphate 5-kinase with the consequent production of PA and PIP2, respectively. In addition to mediating Arf's effects on membrane traffic and the actin cytoskeleton, PA and PIP2 are involved in the regulation of Arf. Arf also works with Rho family proteins to affect the actin cytoskeleton. Several Arf-binding proteins suspected to be effectors have been identified in two-hybrid screens. Arf-dependent biochemical activities, actin cytoskeleton changes, and membrane trafficking may be integrally related. Understanding Arf's role in complex cellular functions such as protein secretion or cell movement will involve a description of the temporal and spatial coordination of these multiple Arf-dependent events.
-
[
Environ Pollut,
2022]
In recent decades, nanotechnology has rapidly developed. Therefore, there is growing concern about the potential environmental risks of nanoparticles (NPs). Caenorhabditis elegans (C. elegans) has been used as a powerful tool for studying the potential ecotoxicological impacts of nanomaterials from the whole animal level to single cell level, especially in the area of reproduction. In this review, we discuss the reproductive toxicity of common nanomaterials in C. elegans, such as metal-based nanomaterial (silver nanoparticles (NPs), gold NPs, zinc oxide NPs, copper oxide NPs), carbon-based nanomaterial (graphene oxide, multi-walled carbon nanotubes, fullerene nanoparticles), polymeric NPs, silica NPs, quantum dots, and the potential mechanisms involved. This insights into the toxic effects of existing nanomaterials on the human reproductive system. In addition, we summarize how the physicochemical properties (e.g., size, charge, surface modification, shape) of nanomaterials influence their reproductive toxicity. Overall, using C. elegans as a platform to develop rapid detection techniques and prediction methods for nanomaterial reproductive toxicity is expected to reduce the gap between biosafety evaluation of nanomaterials and their application.
-
[
Biochem J,
2008]
DGKs (diacylglycerol kinases) are members of a unique and conserved family of intracellular lipid kinases that phosphorylate DAG (diacylglycerol), catalysing its conversion into PA (phosphatidic acid). This reaction leads to attenuation of DAG levels in the cell membrane, regulating a host of intracellular signalling proteins that have evolved the ability to bind this lipid. The product of the DGK reaction, PA, is also linked to the regulation of diverse functions, including cell growth, membrane trafficking, differentiation and migration. In multicellular eukaryotes, DGKs provide a link between lipid metabolism and signalling. Genetic experiments in Caenorhabditis elegans, Drosophila melanogaster and mice have started to unveil the role of members of this protein family as modulators of receptor-dependent responses in processes such as synaptic transmission and photoreceptor transduction, as well as acquired and innate immune responses. Recent discoveries provide new insights into the complex mechanisms controlling DGK activation and their participation in receptor-regulated processes. After more than 50 years of intense research, the DGK pathway emerges as a key player in the regulation of cell responses, offering new possibilities of therapeutic intervention in human pathologies, including cancer, heart disease, diabetes, brain afflictions and immune dysfunctions.
-
[
J Neurosci Res,
2010]
The neuromuscular junction (NMJ) of Caenorhabditis elegans has proved to be a very useful model synapse for investigating molecular mechanisms of synaptic transmission. Intriguingly, miniature postsynaptic currents (minis) at this synapse occur at an unusually high frequency (50-90 Hz in wild-type worms) and show large variation in quantal size (from <10 pA to >200 pA). It is important to understand the cellular and molecular bases for these properties of minis in order to interpret electrophysiological data from this synapse properly. Existing data suggest that several factors may contribute to the high frequency and quantal size variation, including 1) the establishment of multiple NMJs with each body-wall muscle cell, 2) diversity of postsynaptic receptors (two acetylcholine receptors and one GABA receptor), 3) association of one presynaptic site with several body-wall muscle cells, 4) effects of Ca(2+) at the presynaptic site, and 5) a possibly elevated (less negative) resting membrane potential in motoneurons. Neither the frequency nor the quantal size of minis is affected by electrical coupling of body-wall muscle cells. Furthermore, quantal size variation is not due to synchronized multivesicular release. Analyses of the C. elegans NMJ may lead to a better understanding of the mechanisms controlling the frequency and quantal size of minis of other synapses as well.
-
[
Metallomics,
2014]
Phytochelatins are sulfur-rich metal-binding peptides, and phytochelatin synthesis is one of the key mechanisms by which plants protect themselves against toxic soft metal ions such as cadmium. It has been known for a while now that some invertebrates also possess functional phytochelatin synthase (PCS) enzymes, and that at least one species, the nematode Caenorhabditis elegans, produces phytochelatins to help detoxify cadmium, and probably also other metal and metalloid ions including arsenic, zinc, selenium, silver, and copper. Here, we review recent studies on the occurrence, utilization, and regulation of phytochelatin synthesis in invertebrates. The phytochelatin synthase gene has a wide phylogenetic distribution, and can be found in species that cover almost all of the animal tree of life. The evidence to date, though, suggests that the occurrence is patchy, and even though some members of particular taxonomic groups may contain PCS genes, there are also many species without these genes. For animal species that do possess PCS genes, some of them (e.g. earthworms) do synthesize phytochelatins in response to potentially toxic elements, whereas others (e.g. Schistosoma mansoni, a parasitic helminth) do not appear to do so. Just how (and if) phytochelatins in invertebrates complement the function of metallothioneins remains to be elucidated, and the temporal, spatial, and metal specificity of the two systems is still unknown.