Shina MC et al. (2008) Subcell Biochem "Invertebrate coronins."

Noegel AA, Shina MC

[Subcell Biochem, 2008]

Coronins are highly conserved among species, but their function is far from being understood in detail. Here we will introduce members of the family of coronin like proteins from Drosophila melanogaster, Caenorhabditis elegans and the social amoeba Dictyostelium discoideum. Genetic data from D. discoideum and D. melanogaster revealed that coronins in general are important regulators of many actin-dependent processes.

Raghu P et al. (2009) Biochim Biophys Acta "Emerging findings from studies of phospholipase D in model organisms (and a short update on phosphatidic acid effectors)."

Raghu P, Coadwell J, Ktistakis NT, Manifava M

[Biochim Biophys Acta, 2009]

Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine to generate phosphatidic acid and choline. Historically, much PLD work has been conducted in mammalian settings although genes encoding enzymes of this family have been identified in all eukaryotic organisms. Recently, important insights on PLD function are emerging from work in yeast, but much less is known about PLD in other organisms. In this review we will summarize what is known about phospholipase D in several model organisms, including C. elegans, D. discoideum, D. rerio and D. melanogaster. In the cases where knockouts are available (C. elegans, Dictyostelium and Drosophila) the PLD gene(s) appear not to be essential for viability, but several studies are beginning to identify pathways where this activity has a role. Given that the proteins in model organisms are very similar to their mammalian counterparts, we expect that future studies in model organisms will complement and extend ongoing work in mammalian settings. At the end of this review we will also provide a short update on phosphatidic acid targets, a topic last reviewed in 2006.

Schierenberg E et al. (1992) Seminars in Developmental Biology "The establishment of embryonic axes and determination of cell fates in embryos of the nematode Caenorhabditis elegans."

Schierenberg E, Strome S

[Seminars in Developmental Biology, 1992]

At the 4-cell stage of the C. elegans embryo, three axes can be defined: anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R). The A-P axis first becomes obvious in the newly fertilized 1-cell embryo. Pronouned cytoplasmic assymmetries arise along the A-P axis during the first cell cycle, after which the zygote undergoes a series of stem cell-like cleavages with an A-P orientation of the mitotic spindle; these cleavages generate several somatic founder cells and a primordial germ cell. The D-V and L-R axes are defined by the direction of spindle rotation as the 2-cell embryo divides into four cells. In contrast to the A-P axis, there do not appear to be cellular asymmetries associated with the D-V and L-R axes, and both axes can easily be reversed by micromanipulation. Thus, with respect to the roles that the embryonic axes serve in cell-fate determination in the early C. elegans embryo, it appears that internally transmitted developmental information is differentially segregated along the A-P axis, but not along the D-V or L-R axes. Instead, D-V and L-R differences in the fates of cells within lineages appear to be dictated by differential

Furukawa K et al. (2002) Biochim Biophys Acta "Galactosyltransferase I is a gene responsible for progeroid variant of Ehlers-Danlos syndrome: molecular cloning and identification of mutations."

Furukawa K, Okajima T

[Biochim Biophys Acta, 2002]

A human cDNA encoding a novel galactosyltransferase was identified based on BLAST analysis of expressed sequence tags, and the cDNA clones were isolated, showing a type II membrane protein with 327 amino acids and 38% homology to the Caenorhabditis elegans sqv-3 gene involved in vulval invagination and oocyte development. This cDNA exhibited marked galactosyltransferase activity specific for p-nitrophenyl-beta-D-xylopyranoside, and also restored glycosaminoglycan (GAG) synthesis to galactosyltransferase I-deficient CHO mutant pgsB-761 cells. The enzyme product contained beta-1,4-linked galactosyl residues, indicating that the enzyme is galactosyltransferase I (UDP-D-galactose: D-xylose beta-1,4-D-galactosyltransferase; EC 2.4.1.133) involved in the synthesis of the GAG-protein linkage region of proteoglycans. Mutations of this gene were investigated in a case of Ehlers-Danlos syndrome (progeroid variant), since reduced activity of galactosyltransferase I had been reported in this disease by others. As expected, the patient gene contained two different mutations (A186D, L206P). The mutations showed, respectively, 10-50% and 0% of the enzyme activity compared with wild type, suggesting that galactosytransferase I (XGal-T1) is at least one of the genes responsible for Ehlers-Danlos syndrome (progeroid variant).

Tatar M et al. (2001) Experimental Gerontology "Slow aging during insect reproductive diapause: why butterflies, grasshoppers and flies are like worms"

Yin C, Tatar M

[Experimental Gerontology, 2001]

Diapause is a state of arrested development accompanied by physiology for somatic persistence. Diapause is common in many invertebrates and is familiar to biogerontology in the context of Caenorhabditis elegans dauer. Among insects, diapause may occur in embryos, larvae, pupae or adults. At the adult stage, reproductive diapause arrests development of oogenesis, vitellogenesis, accessory gland activity, and mating behavior. Reproductive diapause has been well studied in monarch butterflies, several grasshoppers, and several Diptera, including Drosophila and Phormia. In monarchs and in grasshoppers, reproductive diapause physiology has been experimentally induced by the surgical removal of the corpora allata, the source of adult juvenile hormone; allatectomy in each case was found to double adult longevity. Among Drosophila, the endemic D. triauraria of Japan, and D. littoralis of Finland over-winter as adults in reproductive diapause. How D. melanogaster winter is poorly understood, but reproductive diapause can be cued by cool temperature. In laboratory studies, the mortality rates of post-diapause D. melanogaster are similar to rates of newly enclosed, young flies. This implies that senescence during diapause is slow or negligible. Slow aging during the diapause period may involve elevated somatic stress resistance as well as reallocation of resources to somatic maintenance. Reproductive diapause in Drosophila is proximally controlled by down regulation of juvenile hormone, a phenotype that is also produced by mutants of the insulin-like receptor InR, homologue of C. elegans daf-2. We propose neuroendocrine control of reproductive diapause in D. melanogaster that includes phenotypic plasticity for rates of senescence.

Kemphues KJ (2000) Cell "PARsing embryonic polarity."

Kemphues KJ

[Cell, 2000]

Current understanding of the way in which embryonic polarity is established relies heavily on studies of maternal effect lethal mutants in D. melanogaster and C. elegans. Although the analysis in worms began in earnest about a decade after the explosion of information from flies, we now know enough about both systems to make comparisons meaningful, and to ask whether there are conserved mechanisms used for establishing embryonic polarity. Thus far, the single common feature is translational repression, which has been shown to localize important fate regulators in both systems. Now, however, in this issue of Cell, Shulman and colleagues report an analysis in D. melanogaster of the first molecule to play an important and perhaps conserved role in both animals, PAR-1.

Schachter H (2010) Semin Cell Dev Biol "Mgat1-dependent N-glycans are essential for the normal development of both vertebrate and invertebrate metazoans."

Schachter H

[Semin Cell Dev Biol, 2010]

UDP-GlcNAc:alpha3-D-mannoside beta1,2-N-acetylglucosaminyltransferase I (GnTI, encoded by Mgat1) first appeared in evolution at about the same time as metazoa suggesting that GnTI-dependent glycans are essential for the development of multicellular organisms. This review describes the effects of mutations in the Mgat1 gene on the development of Caenorhabditis elegans, Drosophila melanogaster and mice.

Maxwell PH (2005) Exp Physiol "Hypoxia-inducible factor as a physiological regulator."

Maxwell PH

[Exp Physiol, 2005]

Hypoxia-Inducible Factor (HIF) is a transcription complex which responds to changes in oxygen, providing cells with a master regulator coordinating changes in gene transcription. HIF operates in all mammalian cell types, and is ancient in evolutionary terms - being conserved in C. elegans and D. melanogaster. This review summarises recent insights into the molecular events which link reduced oxygenation to HIF activation, and emerging insights into the extensive role of HIF in a broad range of physiological processes.

Hampson RJ et al. (2011) Recent Pat Endocr Metab Immune Drug Discov "Whole organism based techniques and approaches in early stage oncology drug discovery-patents and trends."

Hampson RJ, Wyatt MD

[Recent Pat Endocr Metab Immune Drug Discov, 2011]

Discovery of new cancer drugs is important for the improvement of disease treatment and management. In addition to the clear medical needs there are also economic considerations: Much drug discovery is performed in the private sector. The high cost of some drug treatments, which can run to tens of thousands of US$ per patient for single courses of therapy has led to the perception of high profitability in the industry. But drug discovery and development is a very expensive and lengthy process, with an ongoing trend of fewer drugs brought to market per dollar invested in R&D Biochemical-based in vitro screens for hosts of targets have produced early stage drug candidates and led to drugs reaching the market, but there remains a great need to evaluate in vivo efficacy, toxicity and potential off-target effects as early as possible in the discovery process. Using whole organisms much earlier in cancer (and other) drug discovery is a potential approach to improve R&D productivity. Here, we provide an overview of recent patenting activity and take a brief look at possible new developments in the field.

Ohtsuki T et al. (2007) IUBMB Life "T-armless tRNAs and elongated elongation factor Tu."

Ohtsuki T, Watanabe Y

[IUBMB Life, 2007]

Most tRNAs share a common secondary structure containing a T arm, a D arm, an anticodon arm and an acceptor stem. However, there are some exceptions. Most nematode mitochondrial tRNAs and some animal mitochondrial tRNAs lack the T arm, which is necessary for binding to canonical elongation factor Tu (EF-Tu). The mitochondria of the nematode Caenorhabditis elegans have a unique EF-Tu, named EF-Tu1, whose structure has supplied clues as to how truncated tRNAs can work in translation. EF-Tu1 has a C-terminal extension of about 60 aa that is absent in canonical EF-Tu. Recent data from our laboratory strongly suggests that EF-Tu1 recognizes the D-arm instead of the T arm by a mechanism involving this C-terminal region. Further biochemical analysis of mitochondrial tRNAs and EF-Tu from the distantly related nematode Trichinella spp. and sequence information on nuclear and mitochondrial DNA in arthropods suggest that T-armless tRNAs may have arisen as a result of duplication of the EF-Tu gene. These studies provide valuable insights into the co-evolution of RNA and RNA-binding proteins. IUBMB Life, 59: 68-75, 2007.