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[
Bioessays,
2002]
Although the centrosome was first described over 100 years ago, we still know relatively little of the molecular mechanisms responsible for its functions. Recently, members of a novel family of centrosomal proteins have been identified in a wide variety of organisms. The transforming acidic coiled-coil-containing (TACC) proteins all appear to play important roles in cell division and cellular organisation in both embryonic and somatic systems. These closely related molecules have been implicated in microtubule stabilisation, acentrosomal spindle assembly, translational regulation, haematopoietic development and cancer progression. In this review, I summarise what we already know of this protein family and will use the TACC proteins to illustrate the many facets that centrosomes have developed during the course of evolution.
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[
Aging Dis,
2016]
Reversible regulation of proteins by reactive oxygen species (ROS) is an important mechanism of neuronal plasticity. In particular, ROS have been shown to act as modulatory molecules of ion channels-which are key to neuronal excitability-in several physiological processes. However ROS are also fundamental contributors to aging vulnerability. When the level of excess ROS increases in the cell during aging, DNA is damaged, proteins are oxidized, lipids are degraded and more ROS are produced, all culminating in significant cell injury. From this arose the idea that oxidation of ion channels by ROS is one of the culprits for neuronal aging. Aging-dependent oxidative modification of voltage-gated potassium (K(+)) channels was initially demonstrated in the nematode Caenorhabditis elegans and more recently in the mammalian brain. Specifically, oxidation of the delayed rectifier KCNB1 (Kv2.1) and of Ca(2+)- and voltage sensitive K(+) channels have been established suggesting that their redox sensitivity contributes to altered excitability, progression of healthy aging and of neurodegenerative disease. Here I discuss the implications that oxidation of K(+) channels by ROS may have for normal aging, as well as for neurodegenerative disease.
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[
Open Biol,
2019]
Glycosylation refers to the covalent attachment of sugar residues to a protein or lipid, and the biological importance of this modification has been widely recognized. While glycosylation in mammals is being extensively investigated, lower level animals such as invertebrates have not been adequately interrogated for their glycosylation. The rich diversity of invertebrate species, the increased database of sequenced invertebrate genomes and the time and cost efficiency of raising and experimenting on these species have enabled a handful of the species to become excellent model organisms, which have been successfully used as tools for probing various biologically interesting problems. Investigation on invertebrate glycosylation, especially on model organisms, not only expands the structural and functional knowledgebase, but also can facilitate deeper understanding on the biological functions of glycosylation in higher organisms. Here, we reviewed the research advances in invertebrate glycosylation, including N- and O-glycosylation, glycosphingolipids and glycosaminoglycans. The aspects of glycan biosynthesis, structures and functions are discussed, with a focus on the model organisms Drosophila and Caenorhabditis. Analytical strategies for the glycans and glycoconjugates are also summarized.
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[
Genetica,
1994]
Studies are reported on a chemoreception mutant which arose in a mutator strain. The mutant sensory neurons do not stain with fluoresceine isothiocyanate (Dyf phenotype), hence the name,
dyf-1, given to the gene it identifies. The gene maps on LGI, 0.4 map units from
dpy-5 on the
unc-11 side. The response of mutant worms to various repellents has been studied and shown to be partially altered. Other chemoreception based behaviors are less affected. The cilia of the sensory neurons of the amphid are shorter than normal and the primary defect may be in the capacity of the sheath cells to secrete the matrix material that fills the space between cilia in the amphid channel. Progress toward the molecular cloning of the gene is also reported. Relevant results from other laboratories are briefly
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[
Curr Biol,
2002]
Ksr has been genetically defined as a component of the Ras/MAP kinase pathway, but its role has been unclear. New studies now provide evidence that Ksr is important for signal transmission within the MAP kinase module, where it apparently acts as a location-regulated scaffold connecting MEK to Raf.
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[
Invert Neurosci,
2018]
Synapses are specialized contact sites that mediate information flow between neurons and their targets. Important physical interactions across the synapse are mediated by synaptic adhesion molecules. These adhesions regulate formation of synapses during development and play a role during mature synaptic function. Importantly, genes regulating synaptogenesis and axon regeneration are conserved across the animal phyla. Genetic screens in the nematode Caenorhabditis elegans have identified a number of molecules required for synapse patterning and assembly. C. elegans is able to survive even with its neuronal function severely compromised. This is in comparison with Drosophila and mice where increased complexity makes them less tolerant to impaired function. Although this fact may reflect differences in the function of the homologous proteins in the synapses between these organisms, the most likely interpretation is that many of these components are equally important, but not absolutely essential, for synaptic transmission to support the relatively undemanding life style of laboratory maintained C. elegans. Here, we review research on the major group of synaptic proteins, involved in the presynaptic machinery in C. elegans, showing a strong conservation between higher organisms and highlight how C. elegans can be used as an informative tool for dissecting synaptic components, based on a simple nervous system organization.
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[
Biochimie,
2001]
Recently the genomic sequences of three multicellular eukaryotes, Caenorhabditis elegans, Drosophila Melanogaster and Arabidopsis thaliana, have been elucidated. A number of cDNAs encoding glycosyltransferases demonstrated to have a role in N-linked glycosylation have already been cloned from these organisms, e.g., GlcNAc transferases and alphal,3-fucosyltransferases. However, many more homologues of glycosyltransferases and other glycan modifying enzymes have been predicted by analysis of the genome sequences, but the predictions of full length open reading frames appear to be particularly poor in Caenorhabditis. The use of these organisms as models in glycobiology may be hampered since they all have N-linked glycosylation repertoires unlike those of mammals. Arabidopsis and Drosophila have glycosylation similar to that of other plants or insects, while our new data from MALDI-TOF analysis of PNGase A-released neutral N-glycans of Caenorhabditis indicate that there exists a range of pauci- and oligomannosidic structures, with up to four fucose residues and up to two O-methyl groups. With all these three 'genetic model organisms', however, much more work is required for a full understanding of their glycobiology.
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[
Cells,
2016]
Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection.
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[
EMBO Rep,
2015]
The regulated release of neurotransmitter occurs via the fusion of synaptic vesicles (SVs) at specialized regions of the presynaptic membrane called active zones (AZs). These regions are defined by a cytoskeletal matrix assembled at AZs (CAZ), which functions to direct SVs toward docking and fusion sites and supports their maturation into the readily releasable pool. In addition, CAZ proteins localize voltage-gated Ca(2+) channels at SV release sites, bringing the fusion machinery in close proximity to the calcium source. Proteins of the CAZ therefore ensure that vesicle fusion is temporally and spatially organized, allowing for the precise and reliable release of neurotransmitter. Importantly, AZs are highly dynamic structures, supporting presynaptic remodeling, changes in neurotransmitter release efficacy, and thus presynaptic forms of plasticity. In this review, we discuss recent advances in the study of active zones, highlighting how the CAZ molecularly defines sites of neurotransmitter release, endocytic zones, and the integrity of synapses.
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[
Genome Biol,
2000]
SUMMARY: The F-box is a protein motif of approximately 50 amino acids that functions as a site of protein-protein interaction. F-box proteins were first characterized as components of SCF ubiquitin-ligase complexes (named after their main components, Skp I, Cullin, and an F-box protein), in which they bind substrates for ubiquitin-mediated proteolysis. The F-box motif links the F-box protein to other components of the SCF complex by binding the core SCF component Skp I. F-box proteins have more recently been discovered to function in non-SCF protein complexes in a variety of cellular functions. There are 11 F-box proteins in budding yeast, 326 predicted in Caenorhabditis elegans, 22 in Drosophila, and at least 38 in humans. F-box proteins often include additional carboxy-terminal motifs capable of protein-protein interaction; the most common secondary motifs in yeast and human F-box proteins are WD repeats and leucine-rich repeats, both of which have been found to bind phosphorylated substrates to the SCF complex. The majority of F-box proteins have other associated motifs, and the functions of most of these proteins have not yet been defined.