Stone AL et al. (1999) J Protein Chem "Structure-function analysis of the ADAM family of disintegrin-like and metalloproteinase-containing proteins (review)."

Sang QX, Stone AL, Kroeger M

[J Protein Chem, 1999]

The ADAMs belong to a disintegrin-like and metalloproteinase-containing protein family that are zinc-dependent metalloproteinases. These proteins share all or some of the following domain structure: a signal peptide, a propeptide, a metalloproteinase, a disintegrin, a cysteine-rich, and an epidermal growth factor (EGF)-like domains, a transmembrane region, and a cytoplasmic tail. ADAMs are widely distributed in many organs, tissues, and cells, such as brain, testis, epididymis, ovary, breast, placenta, liver, heart, lung, bone, and muscle. These proteins are capable of four potential functions: proteolysis, adhesion, fusion, and intracellular signaling. Because the number of ADAM genes has grown rapidly and the biological functions of most members are unclear, this review analyzes the protein structures and functions, their activation and processing, their known and potential activities, and their evolutionary relationships. A sequence alignment of human ADAMs is compiled and their homology and physical data are calculated. The conceivable functions of ADAMs in reproduction, development, and diseases are also discussed.

Coates D et al. (2000) European Worm Meeting "The ADAMs family of C. elegans: what will the new members do?"

Coates D, Daulby J, Hooper NM, Hope IA

[European Worm Meeting, 2000]

ADAMs are a family of integral membrane glycoproteins containing a disintegrin and a metalloprotease domain. The physiological roles of the majority of ADAMs have yet to be elucidated, however some mammalian ADAMs are known to be involved in many diverse processes including sperm migration, sperm-egg binding and fusion, myoblast fusion, the processing of adhesion molecules, cytokines, cytokine receptors and extracellular protein domains, and in neural development. In C. elegans ADAMs are thought to be involved in cell fusion events in sperm and in epithelial cells (ADM-1), in early embryonic development (ADM-2) and in vulval development (SUP-17). In addition to these membrane anchored proteins C. elegans also has soluble ADAM-like proteases, for example GON-1, which plays an essential role in gonadal morphogenesis. We have identified four novel ADAM-like sequences in C. eleganswhich encode a TNFa converting enzyme (TACE) homologue and three soluble ADAM-like proteinases, and our aim is to determine the precise functions of these proteins. Initially we will examine their cellular location with reporter gene constructs and assess the importance of these proteinases by generating gene knockout mutants. We are also interested in finding out what the substrates of these ADAMs are and will biochemically characterise the recombinant proteins. The data we will attain will be related to the ADAM homologues found in humans.

Crawley M et al. (1998) Worm Breeder's Gazette "Correction"

Adams D, Crawley M

[Worm Breeder's Gazette, 1998]

Correction: "The abstract entitled Control of Mitochondrial Morphology published in WBG Vol. 15 No. 1 contained an error. Worms were treated with 3 mM (not 100 mM) chloramphenicol to induce changes in mitochondrial morphology. Thanks to A.L. for spotting the error. M. Crawley & D. Adams

Adir V et al. (1997) International C. elegans Meeting "ADM-2 A NEW MEMBER OF THE ADAM FAMILY WITH AN ACTIVE METALLOPROTEASE DOMAIN"

Podbilewicz B, Adir V

[International C. elegans Meeting, 1997]

The ADAMs gene family encodes transmembrane proteins which contain both disintegrin and metalloprotease domains. Some ADAMs have a metalloprotease like domain but lack the active site, while others have a consensus active site sequence for a zinc dependent metalloprotease as in snake venoms. The ADAMs gene family includes fertilin a and b (involved in sperm-egg fusion), meltrin-a (required for myotube formation in mice), TACE (a TNF-a converting enzyme), and KUZ (the kuzbanian gene product essential for neural fate in Drosophila). Other members of this family may be involved in different cell-cell and cell-matrix interactions. ADM-1, was the first gene from this family found in C. elegans, and is expressed in cells that undergo cell fusion. However, ADM-1 lacks the consensus active site sequence for a zinc dependent metalloprotease. In order to identify new genes related to the ADAMs gene family in C. elegans, we used the TBLASTN algorithm and found the cDNA clone yk35e9 which encodes adm-2. Alignment of ADM-2 with the metalloprotease domains of other ADAMs, shows that the consensus active site is highly conserved. adm-2 was mapped to YACs Y50F10 and Y49B10 and to the cosmid C04A11. Consensus HEXXHXXGXXH- ADM-2 HELGHDFGNDHD fertilin a HELGHNLGIRHD (Blobel et al., Nature, 1992) meltrin a HELGHNFGMNHD (Yagami Hiromasa et al., Nature, 1995) TACE HELGHNFGAEHD (Black et al., Nature, 1997) KUZ HEIGHNFGSPHD (Rooke et al., Science, 1996) adamalysin HELGHNLGMEHD (Gomis-Ruth et al., EMBO J., 1993) ADM-1 QSIGHLLGLEHD (Podbilewicz, Mol. Biol. Cell, 1996) Alignment of the consensus active sites for zinc-dependent metalloproteases and ADM-1. To study the function of adm-2 and its effect on C. elegans development we inject adm-2 antisense RNA into wild type nematodes. We also perform rescue experiments to candidate mutants that mapped genetically to the genome location of adm-2.

Joanna Daulby et al. (2001) International C. elegans Meeting "Expression of C. elegans ADAM proteins in a mammalian system."

Nigel M Hooper, Joanna Daulby, David Coates, Ian A Hope

[International C. elegans Meeting, 2001]

ADAMs are integral membrane proteins which contain a d isintegrin a nd m etalloprotease domain, and have the potential to participate in proteolysis, adhesion, fusion and signaling events. So far thirty ADAM genes have been described from across the animal kingdom, but their precise functions and mechanisms remain largely unknown. A small number of mammalian ADAMs however, have been shown to be important in development, signal transduction, sperm and egg binding and muscle cell fusion. In addition, some C. elegans ADAMs have been investigated recently and these are thought to be involved in sperm and epithelial cell fusion events ( adm-1 ), in early embryonic development ( adm-2 ), and in vulval development ( sup-17 ). C. elegans also possesses homologues of ADAM-like genes known as ADAM-TS. Proteins encoded by this gene family are not membrane bound and have an additional thrombospondin-like motif, for example GON-1 and MIG-17. These proteins play essential roles in the morphogenesis of the C. elegans gonad. We are studying three other ADAMs genes in C. elegans : adm-4 (a tumour necrosis factor alpha converting enzyme or TACE homologue); and two soluble ADAM-TSs, ( C02B4.1 and T19D2.1 ). GFP reporter data indicates that adm-4 is highly expressed in most tissues in all post-embryonic stages. The expression pattern for C02B4.1 :: GFP however is more confined and is observed in body wall and pharyngeal muscle. We aim to complement the reporter data with RNAi/knockout mutagenesis work, but our main goal is to biochemically analyse the recombinant proteins in a mammalian expression system. Using this approach we hope to identify which proteins are cleaved by these ADAMs proteins, as well as providing information about their targeting and processing. Ultimately we hope to elucidate their physiological function and relate this information to mammalian ADAM proteins.

Samuel ADT et al. (2003) J Neurosci "Synaptic activity of the AFD neuron in Caenorhabditis elegans correlates with thermotactic memory."

Murthy VN, Samuel ADT, Silva RA

[J Neurosci, 2003]

Thermotactic behavior in Caenorhabditis elegans is sensitive to both a worm's ambient temperature (T-amb) and its memory of the temperature of its cultivation (T-cult). The AFD neuron is part of a neural circuit that underlies thermotactic behavior. By monitoring the fluorescence of pH-sensitive green fluorescent protein localized to synaptic vesicles, we measured the rate of the synaptic release of AFD in worms cultivated at temperatures between 15 and 25degreesC, and subjected to fixed, ambient temperatures in the same range. We found that the rate of AFD synaptic release is high if either T-amb > T-cult or T-amb > T-cult, but AFD synaptic release is low if T-amb congruent to T-cult. This suggests that AFD encodes a direct comparison between T-amb and T-cult.

Bommireddy R et al. (2007) Trends Mol Med "TGFbeta1 and Treg cells: alliance for tolerance."

Bommireddy R, Doetschman T

[Trends Mol Med, 2007]

Transforming growth factor beta1 (TGFbeta1), an important pleiotropic, immunoregulatory cytokine, uses distinct signaling mechanisms in lymphocytes to affect T-cell homeostasis, regulatory T (T(reg))-cell and effector-cell function and tumorigenesis. Defects in TGFbeta1 expression or its signaling in T cells correlate with the onset of several autoimmune diseases. TGFbeta1 prevents abnormal T-cell activation through the modulation of Ca(2+)-calcineurin signaling in a Caenorhabditis elegans Sma and Drosophila Mad proteins (SMAD)3 and SMAD4-independent manner; however, in T(reg) cells, its effects are mediated, at least in part, through SMAD signaling. TGFbeta1 also acts as a pro-inflammatory cytokine and induces interleukin (IL)-17-producing pathogenic T-helper cells (T(h) IL-17 cells) synergistically during an inflammatory response in which IL-6 is produced. Here, we will review TGFbeta1 and its signaling in T cells with an emphasis on the regulatory arm of immune tolerance.

Agulnik SI et al. (1995) Genomics "Conservation of the T-box gene family from Mus musculus to Caenorhabditis elegans."

Bollag RJ, Silver LM, Agulnik SI

[Genomics, 1995]

Recently, a novel family of genes with a region of homology to the mouse T locus, which is known to play a crucial, and conserved, role in vertebrate development, has been discovered. The region of homology has been named the T-box. The T-box domain of the prototypical T locus product is associated with sequence-specific DNA binding activity. In this report, we have characterized four members of the T-box gene family from the nematode Caenorhabditis elegans. All lie in close proximity to each other in the middle of chromosome III. Homology analysis among all completely sequenced T-box products indicates a larger size for the conserved T-box domain (166 to 203 residues) than previously reported. Phylogenetic analysis suggests that one C. elegans T-box gene may be a direct ortholog of the mouse Tbx2 and Drosophila omb genes. The accumulated data demonstrate the ancient nature of the T-box gene family and suggest the existence of at least three separate T-box-containing genes in a common early metazoan ancestor to nematodes and vertebrates.

Ju T et al. (2006) Glycobiology "Identification of core 1 O-glycan T-synthase from Caenorhabditis elegans."

Ju T, Zheng Q, Cummings RD

[Glycobiology, 2006]

The common O-glycan core structure in animal glycoproteins is the core 1 disaccharide Galbeta1-3GalNAcalpha1-Ser/Thr, which is generated by addition of Gal to GalNAcalpha1-Ser/Thr by core 1 UDP-Gal:GalNAcalpha1-Ser/Thr beta1,3-galactosyltransferase (core 1 beta3-Gal-T or T-synthase, EC2.4.1.122)(2). Although O-glycans play important roles in vertebrates, much remains to be learned from model organisms such as the free-living nematode Caenorhabditis elegans, which offer many advantages in exploring O-glycan structure/function. Here we report the cloning and enzymatic characterization of T-synthase from C. elegans (Ce-T-synthase). A putative C. elegans gene for T-synthase, C38H2.2, was identified in GenBank by a BlastP search using the human T-synthase protein sequence. The full-length cDNA for Ce-T-synthase, which was generated by PCR using a C. elegans cDNA library as the template, contains 1,170 bp including the stop TAA. The cDNA encodes a protein of 389 amino acids with typical type-II membrane topology and a remarkable 42.7% identity to the human T-synthase. Ce-T-synthase has 7 Cys residues in the lumenal domain including 6 conserved Cys residues in all of the orthologs. The Ce-T-synthase has 4 potential N-glycosylation sequons, whereas the mammalian orthologs lack N-glycosylation sequons. Only one gene for Ce-T-synthase was identified in the genome-wide search and it contains 8 exons. Promoter analysis of the Ce-T-synthase using green fluorescent protein constructs show that the gene is expressed at all developmental stages and appears to be in all cells. Unexpectedly, only minimal activity was recovered in the recombinant, soluble Ce-T-synthase secreted from a wide variety of mammalian cell lines, whereas robust enzyme activity was recovered in the soluble Ce-T-synthase expressed in Hi-5 insect cells. Vertebrate T-synthase requires the molecular chaperone Cosmc, but our results show that Ce-T-synthase does not require Cosmc, and might require invertebrate-specific factors for formation of the optimally active enzyme. These results show that the Ce-T-synthase is a functional ortholog to the human T-synthase in generating core 1 O-glycans and opens new avenues to explore O-glycan function in this model organism.

Muir RE et al. (2007) Int J Syst Evol Microbiol "Leucobacter chromiireducens subsp. solipictus subsp. nov., a pigmented bacterium isolated from the nematode Caenorhabditis elegans, and emended description of L. chromiireducens."

Muir RE, Tan MW

[Int J Syst Evol Microbiol, 2007]

A yellow-pigmented, Gram-positive, aerobic, non-motile, non-spore-forming, irregular rod-shaped bacterium (strain TAN 31504(T)) was isolated from the bacteriophagous nematode Caenorhabditis elegans. Based on 16S rRNA gene sequence similarity, DNA G+C content of 69.5 mol%, 2,4-diaminobutyric acid in the cell-wall peptidoglycan, major menaquinone MK-11, abundance of anteiso- and iso-fatty acids, polar lipids diphosphatidylglycerol and phosphatidylglycerol and a number of shared biochemical characteristics, strain TAN 31504(T) was placed in the genus Leucobacter. DNA-DNA hybridization comparisons demonstrated a 91 % DNA-DNA relatedness between strain TAN 31504(T) and Leucobacter chromiireducens LMG 22506(T) indicating that these two strains belong to the same species, when the recommended threshold value of 70 % DNA-DNA relatedness for the definition of a bacterial species by the ad hoc committee on reconciliation of approaches to bacterial systematics is considered. Based on distinct differences in morphology, physiology, chemotaxonomic markers and various biochemical characteristics, it is proposed to split the species L. chromiireducens into two novel subspecies, Leucobacter chromiireducens subsp. chromiireducens subsp. nov. (type strain L-1(T)=CIP 108389(T)=LMG 22506(T)) and Leucobacter chromiireducens subsp. solipictus subsp. nov. (type strain TAN 31504(T)=DSM 18340(T)=ATCC BAA-1336(T)).