Maria Martinez-Iniesta et al. (2008) European Worm Meeting "Identification of response and resistance genes to 5-fluroracil (5-FU) in Caenorhabditis elegans."

Maria Martinez-Iniesta, Xavi Sole, Nuria Baixeras, Alberto Villanueva, Laura Padulles, Ramon Salazar, Victor Moreno, J Ramon Germa, Gabriel Capella

[European Worm Meeting, 2008]

Introduction: Colorectal cancer (CRC) is one of the leading causes of. cancer-related mortality in the Western world. In Spain is the second type. of cancer in incidence and mortality in both sexes and 50% of total. diagnostic cases death. Despite the improvement of diagnostic and treatment. only a few decreases have been observed. About 60% of all patients. diagnosed with CRC will present localized disease, being the surgery the. mainstay therapy. The rest of patients (Duke''s C and D) are diagnosed with. distal metastasis. 5-FU and oxaliplatin based chemotherapy (QT) are the. base of the standard treatment of colorectal cancer patients in both. adjuvant and metastasic setting. Initially, more patients did not respond. to QT treatments and others relapse after a short period of response. In. spite of the clinical relevance of 5-FU, little is known about the. mechanisms of resistance to this drug commonly observed in colorectal. cancer patients. Aim: To identify the genes involved in the mechanism of. resistance to 5-FU in the pluricellular model organisms Caenorhabditis. elegans (C.elegans), and posterior validation of these genes as a markers. of response/sensitivity to 5-FU chemotherapy treatments in tumor series.. Methods and Results: A 5-FU plate toxicity assay has been established. We. are characterizing the ceTS-1 gene, C.elegans homolog of human thymidylate. synthase gene, and temporal and cellular expression patterns during. development are studying in GFP transgenic worms. Different alternative. splicing isoforms are generating in CeTS-1 with unknown biological. implications that we are evaluating. Different phenotypes have been. associated with the worm 5-FU treatment. N2 wild-type worms and cib-1(e300). mutant, harboring a point mutation in Thymidilate Synthase gene (Schnabel. R), were synchronized, and both strains of worms were growth at different. drug concentrations and at different times. Profiles of 5-FU response are. being determined in C.elegans Affymetrix microarrays. To identify response. genes (we expected around 100-150 genes) we are performing a feeding double-. stranded RNA-mediated interference (dsRNAi) screening for response genes.. Conclusions: Identification in C. elegans of genes involved in the. resistance/sensitivity to 5-FU drug and later validation of their. predictive value of response in colorectal cancer series may permit to. dispose of the some genetic markers that finally can improve the CRC. patient treatment.. avillanueva@iconcologia.net

Saunders AM et al. (2007) Curr Biol "Kinesin-5 acts as a brake in anaphase spindle elongation."

Strome S, Saunders AM, Saxton WM, Powers J

[Curr Biol, 2007]

Bipolar kinesin-5 motors, essential in diverse organisms, can generate positive sliding forces between overlapped interpolar microtubules to push mitotic spindle poles apart. BMK-1, the sole Caenorhabditis elegans kinesin-5, is not essential. We have determined, by tracking pole movements in bmk-1 mutant C. elegans embryos, that BMK-1 actually resists pole separation during anaphase. This provides in vivo evidence that kinesin-5, when challenged by fast pole separation forces, can serve as a rate-limiting brake for interpolar microtubule sliding.

Pinnock CB et al. (1975) Proc. Society for Experimental Biology & Medicine "Stimulatory effects of peptides on growth of the free-living nematode C. briggsae."

Stokstad ELR, Pinnock CB, Shane B

[Proc. Society for Experimental Biology & Medicine, 1975]

Evidence is presented that peptide products of hydrolysis of casein, including some di- and tripeptides, but not the constituent amino acids, can stimulate growth of C. briggsae in defined basal medium supplemented with cytochrome C and B-sitosterol. Peptide activity may raise from amino acid imbalances in the medium which causes competitive inhibition of uptake of essential amino acids. Such activity precludes facilitation of heme transport as the sole function of growth factor in C. briggsae. This is the first report in a nutritional role of peptides in invertebrate metazoa.

Shida T et al. (2010) Proc Natl Acad Sci U S A "The major alpha-tubulin K40 acetyltransferase alphaTAT1 promotes rapid ciliogenesis and efficient mechanosensation."

Xu Z, Goodman MB, Cueva JG, Shida T, Nachury MV

[Proc Natl Acad Sci U S A, 2010]

Long-lived microtubules found in ciliary axonemes, neuronal processes, and migrating cells are marked by -tubulin acetylation on lysine 40, a modification that takes place inside the microtubule lumen. The physiological importance of microtubule acetylation remains elusive. Here, we identify a BBSome-associated protein that we name TAT1, with a highly specific -tubulin K40 acetyltransferase activity and a catalytic preference for microtubules over free tubulin. In mammalian cells, the catalytic activity of TAT1 is necessary and sufficient for -tubulin K40 acetylation. Remarkably, TAT1 is universally and exclusively conserved in ciliated organisms, and is required for the acetylation of axonemal microtubules and for the normal kinetics of primary cilium assembly. In Caenorhabditis elegans, microtubule acetylation is most prominent in touch receptor neurons (TRNs) and MEC-17, a homolog of TAT1, and its paralog TAT-2 are required for -tubulin acetylation and for two distinct types of touch sensation. Furthermore, in animals lacking MEC-17, TAT-2, and the sole C. elegans K40-tubulin MEC-12, touch sensation can be restored by expression of an acetyl-mimic MEC-12[K40Q]. We conclude that TAT1 is the major and possibly the sole -tubulin K40 acetyltransferase in mammals and nematodes, and that tubulin acetylation plays a conserved role in several microtubule-based processes.

Barker TJ et al. (2023) MicroPubl Biol "Apical-basal polarity of the spectrin cytoskeleton in the C. elegans vulva."

Carvalho AX, Chan FY, Sundaram MV, Barker TJ

[MicroPubl Biol, 2023]

The <i>C. elegans</i> vulva is a polarized epithelial tube that has been studied extensively as a model for cell-cell signaling, cell fate specification, and tubulogenesis. Here we used endogenous fusions to show that the spectrin cytoskeleton is polarized in this organ, with conventional beta-spectrin ( UNC-70 ) found only at basolateral membranes and beta heavy spectrin ( SMA-1 ) found only at apical membranes. The sole alpha-spectrin ( SPC-1 ) is present at both locations but requires SMA-1 for its apical localization. Thus, beta spectrins are excellent markers for vulva cell membranes and polarity.

Fionda V et al. (2009) Int J Data Min Bioinform "A technique to search for functional similarities in protein-protein interaction networks."

Palopoli L, Fionda V, Panni S, Rombo SE

[Int J Data Min Bioinform, 2009]

We describe a method to search for similarities across protein-protein interaction networks of different organisms. The technique core consists in computing a maximum weight matching of bipartite graphs resulting from comparing the neighbourhoods of proteins belonging to different networks. Both quantitative and reliability information are exploited. We tested the method on the networks of S. cerevisiae, D. melanogaster and C. elegans. The experiments showed that the technique is able to detect functional orthologs when the sole sequence similarity does not prove itself sufficient. They also demonstrated the capability of our approach in discovering common biological processes involving uncharacterised proteins.

Matsunaga Y et al. (2012) Biosci Biotechnol Biochem "A Caenorhabditis elegans insulin-like peptide, INS-17: its physiological function and expression pattern."

Kawano T, Matsunaga Y, Iwasaki T, Nakajima K, Mitani S, Gengyo-Ando K

[Biosci Biotechnol Biochem, 2012]

The insulin/insulin-like growth factor-1 signaling pathway of Caenorhabditis elegans regulates larval diapause and adult lifespan through the sole insulin receptor-like protein, DAF-2. In the present study, the physiological function and expression pattern of INS-17, one of the C. elegans insulin-like peptides, were examined by disruption and overexpression of the gene, and by the use of a reporter gene. INS-17 might function as a DAF-2 antagonist in the regulation of larval diapause, but not of the adult lifespan. The reporter protein was intensively expressed during larval diapause. It showed a drastic decrease in amount after larval diapause, which matches well the physiological function of INS-17.

Voutev R et al. (2009) FEBS Lett "Characterization of the Caenorhabditis elegans Islet LIM-homeodomain ortholog, lim-7."

Vallier LG, Jane Albert Hubbard E, Keating R, Voutev R

[FEBS Lett, 2009]

lim-7 is one of seven Caenorhabditis elegans LIM-homeodomain (LIM-HD)-encoding genes and the sole Islet ortholog. LIM-HD transcription factors, including Islets, function in neuronal and non-neuronal development across diverse phyla. Our results show that a lim-7 deletion allele causes early larval lethality with terminal phenotypes including uncoordination, detached pharynx, constipation and morphological defects. A lim-7(+) transgene rescues lethality but not adult sterility. A lim-7(+) reporter in the full genomic context is expressed in all gonadal sheath cells, URA neurons, and additional cells in the pharyngeal region. Finally, we identify a 45-bp regulatory element in the first intron that is necessary and sufficient for lim-7 gonadal sheath expression.

Latorre I et al. (2015) Genes Dev "The DREAM complex promotes gene body H2A.Z for target repression."

Chesney MA, Stempor P, Francesconi M, Ahringer J, Appert A, Strome S, Garrigues JM, Latorre I

[Genes Dev, 2015]

The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell cycle genes, but its mechanism of action is poorly understood. Here we show that Caenorhabditis elegans DREAM targets have an unusual pattern of high gene body HTZ-1/H2A.Z. In mutants of lin-35, the sole p130/Rb-like gene in C. elegans, DREAM targets have reduced gene body HTZ-1/H2A.Z and increased expression. Consistent with a repressive role for gene body H2A.Z, many DREAM targets are up-regulated in htz-1/H2A.Z mutants. Our results indicate that the DREAM complex facilitates high gene body HTZ-1/H2A.Z, which plays a role in target gene repression.

Yanowitz J (2008) Genetics "Genome integrity is regulated by the Caenorhabditis elegans Rad51D homolog rfs-1."

Yanowitz J

[Genetics, 2008]

Multiple mechanisms ensure genome maintenance including DNA damage repair, suppression of transposition, and telomere length regulation. The mortal germ line (MRT) mutants in C. elegans are defective in maintaining genome integrity and result in a progressive loss of fertility over many generations. Here I show that the him-15 locus, defined by the deficiency eDf25, is allelic to rfs-1, the sole rad-51 paralog group member in C. elegans. The rfs-1/ eDf25 mutant displays a MRT phenotype and mutant animals exhibit features of chromosome fusions prior to the onset of sterility. Unlike other MRT genes, rfs-1 manifests fluctuations in telomere lengths and functions independently of telomerase. These data suggest that rfs-1 is a novel regulator of genome stability.