MT9971

Caenorhabditis elegans

OS10523

Caenorhabditis elegans

Bichai F et al. (2009) Water Res "Protection against UV disinfection of E. coli bacteria and B. subtilis spores ingested by C. elegans nematodes."

Barbeau B, Bichai F, Payment P

[Water Res, 2009]

Nematodes, which occur abundantly in granular media filters of drinking water treatment plants and in distribution systems, can ingest and transport pathogenic bacteria and provide them protection against chemical disinfectants. However, protection against UV disinfection had not been investigated to date. In this study, Caenorhabditis elegans nematodes (wild-type strain N2) were allowed to feed on Escherichia coli OP50 and Bacillus subtilis spores before being exposed to 5 and 40 mJ/cm(2) UV fluences, using a collimated beam apparatus (LP, 254 nm). Sonication (15 W, 60s) was used to extract bacteria from nematode guts following UV exposure in order to assess the amount of ingested bacteria that resisted the UV treatment using a standard culture method. Bacteria located inside the gut of C. elegans were shown to benefit from a significant protection against UV. Approximately 15% of the applied UV fluence of 40 mJ/cm(2) (as typically used in WTP) was found to reach the bacteria located inside nematode guts based on the inactivation of recovered bacteria (2.7 log reduction of E. coli bacteria and 0.7 log reduction of B. subtilis spores at 40 mJ/cm(2)). To our knowledge, this study is the first demonstration of the protection effect of bacterial internalization by higher organisms against UV treatment, using the specific case of E. coli and B. subtilis spores ingested by C. elegans.

Kim H et al. (2004) Nature "SNF-6 is an acetylcholine transporter interacting with the dystrophin complex in Caenorhabditis elegans."

Kim H, McIntire SL, Rogers MJ, Richmond JE

[Nature, 2004]

Muscular dystrophies are among the most common human genetic diseases and are characterized by progressive muscle degeneration. Muscular dystrophies result from genetic defects in components of the dystrophin-glycoprotein complex (DGC), a multimeric complex found in the muscle cell plasma membrane(1). The DGC links the intracellular cytoskeleton to the extracellular matrix and is thought to be important for maintaining the mechanical integrity of muscles(2) and organizing signalling molecules(3). The exact role of the DGC in the pathogenesis of disease has, however, remained uncertain(4). Mutations in Caenorhabditis elegans DGC genes lead to specific defects in coordinated movement and can also cause muscle degeneration(5-7). Here we show that mutations in the gene snf-6 result in phenotypes indistinguishable from those of the DGC mutants, and that snf-6 encodes a novel acetylcholine/choline transporter. SNF-6 mediates the uptake of acetylcholine at neuromuscular junctions during periods of increased synaptic activity. SNF-6 also interacts with the DGC, and mutations in DGC genes cause a loss of SNF-6 at neuromuscular junctions. Improper clearing of acetylcholine and prolonged excitation of muscles might contribute to the pathogenesis of muscular

Strittmatter P et al. (1974) Proc Natl Acad Sci U S A "Purification and properties of rat liver microsomal stearyl coenzyme A desaturase."

Setlow B, Redline R, Corcoran D, Spatz L, Rogers MJ, Strittmatter P

[Proc Natl Acad Sci U S A, 1974]

The terminal enzyme of the NADH-dependent stearyl coenzyme A desaturase system has been isolated from rat liver microsomes. This desaturase is a single polypeptide of 53,000 daltons containing 62% nonpolar amino-acid residues and one atom of non-heme iron. The purified protein forms high molecular weight aggregates that can be dispersed by detergent procedures. Desaturase activity requires NADH, stearyl coenzyme A, oxygen, lipid, and the three enzymes, cytochorme b(5) reductase (EC 1.6.2.2), cytochrome b(5), and desaturase. Cytochrome b(5) is the direct electron donor to the desaturase, which appears to utilize the iron in the oxidation-reduction sequence during desaturation of stearyl coenzyme A.

Rogers, Alicia Kathryn et al. MicroPubl Biol

Rogers, Alicia Kathryn, Phillips, Carolyn Marie

[MicroPubl Biol, 2020]

Mutator foci are perinuclear granules in the germline of Caenorhabditis elegans that are required for the amplification of 22G-small interfering RNAs (siRNAs) (Phillips et al., 2012). These mutator-dependent siRNAs act downstream of primary endogenous and exogenous siRNA pathways and are necessary for robust and heritable silencing (Pak et al., 2007; Sijen et al., 2007; Gu et al., 2009; Gent et al., 2010; Vasale et al., 2010; Phillips et al., 2012). There are numerous factors that have been identified that localize to Mutator foci and are required for mutator-dependent siRNA biogenesis. These mutator-class proteins include the core component of Mutator foci MUT-16, the nucleotidyl transferase MUT-2, the 3-5 exonuclease MUT-7, the DEAD-box RNA helicases MUT-14 and SMUT-1, the Zc3h12a-like ribonucleases RDE-8, NYN-1, and NYN-2, and two proteins of unknown function, MUT-15 and RDE-2 (Ketting et al., 1999; Tijsterman et al., 2002; Vastenhouw et al., 2003; Chen et al., 2005; Tops et al., 2005; Phillips et al., 2012; Phillips et al., 2014; Tsai et al., 2015). Additionally, the RNA-dependent RNA polymerase RRF-1 localizes to Mutator foci but is redundant with EGO-1 for mutator-dependent siRNA biogenesis (Phillips et al., 2012; Gu et al., 2009). It was previously shown that mutations in mutator-class genes are sterile at elevated temperature (Ketting et al., 1999; Zhang et al., 2011; Rogers and Phillips, 2020). Recently, we performed a brood size assay using wild-type and mut-16 hermaphrodites cultured at 20C. We found that compared to wild-type animals, mut-16 mutant animals lay fewer eggs (56% fewer eggs laid compared to wild-type animals), and of those eggs, fewer mut-16 mutant eggs hatch (81% of mut-16 mutant eggs hatch compared to wild-type, where 100% of the eggs hatch) (Rogers and Phillips, 2020). Furthermore, 100% of wild-type larvae successfully mature to adulthood, whereas only 85% of mut-16 mutant larvae mature to adulthood (Rogers and Phillips, 2020). The reduced hatching rates and larval arrest of mut-16 mutant animals had not been previously reported...

Slc2a12

Homo sapiens

SLC2A12 belongs to a family of transporters that catalyze the uptake of sugars through facilitated diffusion (Rogers et al., 2002). This family of transporters show conservation of 12 transmembrane helices as well as functionally significant amino acid residues (Joost and Thorens, 2001 [PubMed 11780753]).[supplied by OMIM, Mar 2008]

Merav Cohen et al. (2003) International Worm Meeting "Genetic dissection of neuropeptide regulation of social feeding"

Merav Cohen, Mario De Bono, Gemma Brown

[International Worm Meeting, 2003]

Neuropeptides are important regulators of behaviour, but the mechanisms underlying their biogenesis and release are poorly understood. To gain general insights into neuropeptide biology we are carrying out genetic dissection of neuropeptide inhibition of aggregation behaviour in C. elegans. Null mutations in the neuropeptide receptor NPR-1 induce strong social feeding behaviour2. NPR-1 is expressed in about 20% of the C. elegans nervous system, and transgenic studies suggest the NPR-1 receptor suppresses social feeding in part by regulating the activity of one or more of the body cavity neurons AQR, PQR and URX3. However NPR-1 activity in other neurons is also likely to contribute to suppressing social feeding3. To identify genes required for release of functional NPR-1 ligands, or that act downstream of the activated NPR-1 receptor, we have sought mutations that convert solitary N2 animals into social feeders. We identifed 8 social mutants from a screen of approximately 4900 genomes. One of the mutants was a new npr-1 allele; the other mutants appear to define new genes. Interestingly, like npr-1 mutants, all of these new social mutants accumulate at the border of the bacterial lawn. The majority also show high locomotory activity on food, another npr-1 phenotype. Genetic and electrophysiological data suggest that NPR-1 is activated by peptide ligands encoded by the flp (FMRFamide-like peptides) genes flp-18 and flp-21 (see abstract by Rogers et al. ). A flp-21 mutant shows very weak social feeding (Rogers et al.), suggesting that a flp-21 deletion background may provide a sensitized background to identify new social mutants. We are therefore repeating the screen in a flp-21 mutant background in an attempt to identify new genes that act upstream or downstream of the NPR-1 receptor. 1 Current address: University of Washington, Seattle; 2 de Bono and Bargmann, 1998, Cell 94: 679-689; 3 Coates and de Bono, Nature 419: 925-929.

Bradford D et al. (2009) Int J Biochem Cell Biol "Netrin-1: diversity in development."

Cole SJ, Bradford D, Cooper HM

[Int J Biochem Cell Biol, 2009]

In 1990, the discovery of three Caenorhabditis elegans genes (unc5, unc6, unc40) involved in pioneer axon guidance and cell migration marked a significant advancement in neuroscience research [Hedgecock EM, Culotti JG, Hall DH. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 1990;4:61-85]. The importance of this molecular guidance system was exemplified in 1994, when the vertebrate orthologue of Unc6, Netrin-1, was discovered to be a key guidance cue for commissural axons projecting toward the ventral midline in the rodent embryonic spinal cord [Serafini T, Kennedy TE, Galko MJ, Mirzayan C, Jessell TM, Tessier-Lavigne M. The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 1994;78:409-424]. Since then, Netrin-1 has been found to be a critical component of embryonic development with functions in axon guidance, cell migration, morphogenesis and angiogenesis. Netrin-1 also plays a role in the adult brain, suggesting that manipulating netrin signals may have novel therapeutic applications.

David S Peal et al. (2003) International Worm Meeting "Negative Regulation of FGF Signaling By Heparan Sulfate in Caenorhabditis elegans"

David S Peal, Laura L Kiessling, Beth Stadtmueller, Judith Kimble

[International Worm Meeting, 2003]

Heparan sulfate (HS) proteoglycans are proteins that display sulfated carbohydrate polymers. HS proteoglycans are implicated in numerous biological processes, including signal transduction and modulation of proteolytic cascades. The 3-O sulfate group found on the N-acetylglucosamine moiety of HS is particularly intriguing. The only known role of this group is to modulate the coagulation cascade in mammals, yet multiple genes encoding 3-O sulfotransferases and their spliced isoforms are expressed in complex and tissue-specific patterns during development. These observations imply that 3-O sulfation may have other functions. To investigate the role of 3-O sulfation, we have isolated a null mutant of the 3-O sulfotransferase (3OST) gene in C. elegans. This mutant is clear (clr) at a low penetrance (35%). This previously described phenotype is caused by upregulation of the FGF signaling pathway(1). Our results suggest that the 3-O sulfate group of HS is involved in negative regulation of FGF signaling. We are testing this hypothesis through genetic and biochemical experiments. (1) Kokel, M, Borland, CZ, DeLong, L, Horvitz, HR, Stern, MJ. Genes Dev 1998; 12: 1425-37.