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FASEB J,
1994]
Two types of collagens have been identified in Caenorhabditis elegans corresponding to two types of extracellular matrix, the cuticle and basement membranes. Cuticle collagens are encoded by a developmentally regulated family of similar to 100 genes. Mutations in cuticle collagens can produce animals that are longer or shorter than normal and/or that are helically twisted. Mutations in different collagens can cause different morphological abnormalities, as can different mutations in the same collagen. Genetic interactions between collagen genes have been described and may identify collagens that interact to form the cuticle. Two basement membrane (type IV) collagen genes have been identified in C. elegans. They encode proteins similar in structure to vertebrate type IV collagen. One of the genes produces two alternatively spliced forms, one predominantly expressed in embryos and the other in larvae and adults, suggesting that embryonic basement membranes may have unique properties. Most mutations in the type IV genes cause embryonic lethality, indicating that normal basement membranes are required for embryogenesis. Temperature-sensitive mutations have been used to show that type IV collagen function is also required for larval development and adult fertility.
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Matrix Biol,
2015]
The members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of secreted proteins, MIG-17 and GON-1, play essential roles in Caenorhabditis elegans gonadogenesis. The genetic and molecular analyses of these proteinases uncovered novel molecular interactions regulating the basement membrane (BM) during the migration of the gonadal leader cells. MIG-17, which is localized to the gonadal BM recruits or activates fibulin-1 and type IV collagen, which then recruits nidogen, thereby inducing the remodeling of the BM that is required for directional control of leader cell migration. GON-1 acts antagonistically with fibulin-1 to regulate the levels of type IV collagen accumulation in the gonadal BM, which facilitates active migration of the leader cells. The cooperative action of MIG-17 and GON-1 represents an excellent model for understanding the mechanisms of organogenesis mediated by ADAMTS proteinases.
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Dev Dyn,
2010]
We review recent studies that have advanced our understanding of the molecular mechanisms regulating transcription in the nematode C. elegans. Topics covered include: (i) general properties of C. elegans promoters; (ii) transcription factors and transcription factor combinations involved in cell fate specification and cell differentiation; (iii) new roles for general transcription factors; (iv) nucleosome positioning in C. elegans "chromatin"; and (v) some characteristics of histone variants and histone modifications and their possible roles in controlling C. elegans transcription.
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Canadian Journal of Zoology,
1988]
Nematodes have a number of biological attributes that make them amenable for molecular studies. In our laboratory, attention has focused on (i) determining the polypeptide composition of cuticles, (ii) using monoclonal antibodies to identify epitopes among the cuticular proteins, (iii) visualizing the sites of collagenous components within the cuticle of Ascaris by immunolocalization, and (iv) sequencing a moderately repetitive DNA element that is found, with extensive similarity, in the genomes of Ascaris and Panagrellus. The role of these and other molecular studies in understanding the biology of nematodes is discussed.
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Parasitol Today,
1991]
The collagen genes of nematodes encode proteins that have a diverse range of functions. Among their most abundant products are the cuticular collagens, which include about 80% of the proteins present in the nematode cuticle. The structures of these collagens have been found to be strikingly similar in the free-living and parasitic nematode species studied so far, and the genes that encode them appear to constitute a large multigene family whose expression is subject to developmental regulation. Collagen genes that may have a role in cell-cell interactions and collagen genes that correspond to the vertebrate type IV collagen genes have also been identified and studied in nematodes.
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Neurosci Biobehav Rev,
1996]
The early embryo orients to the antero-posterior axis and differentiates along this, and the dorso-ventral and lateral axes. From Drosophila melanogaster, detailed knowledge has accrued of how segmentation and dorso-ventral differentiation proceed, and of their genic control, mostly by selector and homeobox (Hox) genes. The study of the control of lateral differentiation, instead, has been largely neglected. Yet handed asymmetry (the "obvious" asymmetries of, for example, heart, lung, anatomical features of the nervous system, etc.) is basic and, possibly, universal. In the mouse, two genes control this: the iv gene which, when mutated, leads to random, in the place of biased, asymmetry and so to random situs inversus viscerum: and the inv mutation which, by contrast, results in 100% situs inversus. Both mutants act as autosomal recessives. Human situs inversus is heterogeneous and may be akin to that produced by the murine iv gene. In spite of situs inversus, there is no shift of hand preference; but there is no information on other lateralization, e.g. of language or of dermatoglyphic patterns. Handed asymmetry is known in Drosophila, but there is no information on its control. In the experimental nematode, Caenorhabditis elegans, asymmetry arises when differently programmed cells arrange themselves to the two body sides, and is present already at the six-cell stage; and even the major sensory neurons chains along the body axis are distributed unequally on the two sides of the worm. Experimentally, by embryonic micro-manipulation or the use of chemical mutagens, the normal and invariate direction of handed asymmetry can be reversed.
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Trends Cell Biol,
2005]
Among the 16 known vertebrate synaptotagmins, only Syt I, IV and VII are also present in C. elegans and Drosophila, suggesting that these isoforms play especially important roles in vivo. Extensive evidence indicates that Syt I is a synaptic vesicle Ca(2+) sensor essential for rapid neurotransmitter release. It has been suggested that the ubiquitously expressed Syt VII also regulates synaptic vesicle exocytosis, despite its presence in several tissues in addition to the brain. Here, we discuss recent genetic and biochemical evidence that does not support this view. Syt VII null mutants do not have a neurological phenotype, and the protein is found on the membrane of lysosomes and some non-synaptic secretory granules, where it regulates Ca(2+)-triggered exocytosis and plasma membrane repair.
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Mutat Res,
2010]
Apurinic/apyrimidinic (AP) endonucleases are versatile DNA repair enzymes that possess a variety of nucleolytic activities, including endonuclease activity at AP sites, 3' phosphodiesterase activity that can remove a variety of ligation-blocking lesions from the 3' end of DNA, endonuclease activity on oxidative DNA lesions, and 3' to 5' exonuclease activity. There are two families of AP endonucleases, named for the bacterial counterparts endonuclease IV (EndoIV) and exonuclease III (ExoIII). While ExoIII family members are present in all kingdoms of life, EndoIV members exist in lower organisms but are curiously absent in plants, mammals and some other vertebrates. Here, we review recent research on these enzymes, focusing primarily on the EndoIV family. We address the role(s) of EndoIV members in DNA repair and discuss recent findings from each model organism in which the enzymes have been studied to date.
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Free Radic Biol Med,
2002]
THE HYPOTHESIS THAT THE RATE OF OXYGEN CONSUMPTION AND THE ENSUING ACCRUAL OF MOLECULAR OXIDATIVE DAMAGE CONSTITUTE A FUNDAMENTAL MECHANISM GOVERNING THE RATE OF AGING IS SUPPORTED BY SEVERAL LINES OF EVIDENCE: (i) life spans of cold blooded animals and mammals with unstable basal metabolic rate (BMR) are extended and oxidative damage (OxD) is attenuated by an experimental decrease in metabolic rate; (ii) single gene mutations in Drosophila and Caenorhabditis elegans that extend life span almost invariably result in a generalized slowing of physiological activities, albeit via different mechanisms, affecting a decrease in OxD; (iii) caloric restriction decreases body temperature and OxD; and, (iv) results of studies on the effects of transgenic overexpressions of antioxidant enzymes are generally supportive, but quite ambiguous. It is suggested that oxidative damage to proteins plays a crucial role in aging because oxidized proteins lose catalytic function and are preferentially hydrolyzed. It is hypothesized that oxidative damage to specific proteins constitutes one of the mechanisms linking oxidative stress/damage and age-associated losses in physiological functions.
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Cell Calcium,
2014]
Members of the Transient Receptor Potential-Mucolipin (TRPML) constitute a family of evolutionarily conserved cation channels that function predominantly in endolysosomal vesicles. Whereas loss-of-function mutations in human TRPML1 were first identified as being causative for the lysosomal storage disease, Mucolipidosis type IV, most mammals also express two other TRPML isoforms called TRPML2 and TRPML3. All three mammalian TRPMLs as well as TRPML related genes in other species including Caenorhabditis elegans and Drosophila exhibit overlapping functional and biophysical properties. The functions of TRPML proteins include roles in vesicular trafficking and biogenesis, maintenance of neuronal development, function, and viability, and regulation of intracellular and organellar ionic homeostasis. Biophysically, TRPML channels are non-selective cation channels exhibiting variable permeability to a host of cations including Na(+), Ca(2+), Fe(2+), and Zn(2+), and are activated by a phosphoinositide species, PI(3,5)P2, that is mostly found in endolysosomal membranes. Here, we review the functional and biophysical properties of these enigmatic cation channels, which represent the most ancient and archetypical TRP channels.