Zafra, Isabella et al. (2021) MicroPubl Biol

Zafra, Isabella, Nebenfuehr, Benjamin, Golden, Andy

[MicroPubl Biol, 2021]

For Zafra, I; Nebenfuehr, B; Golden, A (2021). Saul-Wilson Syndrome Missense Allele Does Not Show Obvious Golgi Defects in a C. elegans Model. microPublication Biology. 10.17912/micropub.biology.000373.

Tan EH et al. (2012) EMBO J "A new tumour suppressor enters the network of intestinal progenitor cell homeostasis."

Tan EH, Sansom OJ

[EMBO J, 2012]

In this issue of The EMBO Journal, Wilson et al (2012) elegantly discovered an important new axis for intestinal homeostasis and cancer, using an RNAi screen to enhance the RAS-induced multivulva (MUV) phenotype in Caenorhabditis elegans.

Sulston JE et al. (1992) Nature "The C. elegans genome sequencing project: a beginning."

Wilson RK, Metzstein MM, Ainscough R, Waterston RH, Coulson AR, Craxton M, Thomas K, Dear S, Qiu L, Staden R, Berks M, Halloran N, Thierry-Mieg J, Hillier L, Sulston JE, Du Z, Durbin RM, Hawkins TL, Green P

[Nature, 1992]

The long-term goal of this project is the elucidation of the complete sequence of the Caenorhabditis elegans genome. During the first year methods have been developed and a strategy implemented that is amenable to large-scale sequencing. The three cosmids sequenced in this initial phase are surprisingly rich in genes, many of which have mammalian homologues.AD - MRC Laboratory of Molecular Biology, Cambridge, UK.FAU - Sulston, JAU - Sulston JFAU - Du, ZAU - Du ZFAU - Thomas, KAU - Thomas KFAU - Wilson, RAU - Wilson RFAU - Hillier, LAU - Hillier LFAU - Staden, RAU - Staden RFAU - Halloran, NAU - Halloran NFAU - Green, PAU - Green PFAU - Thierry-Mieg, JAU - Thierry-Mieg JFAU - Qiu, LAU - Qiu LAU - et al.LA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (Cosmids)SB - IM

Sambongi Y et al. (1997) J Biochem "Caenorhabditis elegans cDNA for a Menkes/Wilson disease gene homologue and its function in a yeast CCC2 gene deletion mutant."

Sambongi Y, Yoshimizu T, Wakabayashi T, Futai M, Oka T, Omote H

[J Biochem, 1997]

The full-length cDNA coding for a putative copper transporting P-type ATPase (Cu2+-ATPase) was cloned from Caenorhabditis elegans. The putative Cu2+-ATPase is a 1,238-amino acid protein, and highly homologous to the Menkes and Wilson disease gene products mutations of which are responsible for human defects of copper metabolism. The Saccharomyces cerevisiae mutant with a disrupted CCC2 gene (yeast Menkes/Wilson disease gene homologue) was rescued by the cDNA for the C. elegans Cu2+-ATPase but not by the cDNA with an Asp-786 (an invariant phosphorylation site) to Asn mutation, suggesting that the C. elegans Cu2+-ATPase functions as a copper transporter in yeast. The expressed C. elegans protein was detected in yeast vacuolar membranes by immunofluorescence microscopy. The yeast expression system may facilitate further studies on copper transporting P-type ATPases.

Zafra, Isabella et al. (2021) MicroPubl Biol

Nebenfuehr, Benjamin, Golden, Andy, Zafra, Isabella

[MicroPubl Biol, 2021]

Saul-Wilson Syndrome (SWS) is an ultra-rare, autosomal dominant skeletal dysplasia syndrome discovered in 1990; only 16 patients have been identified to date (Saul and Wilson 1990; Ferreira et al. 2018, OMIM#: 618150). The disease is characterized by short stature, various craniofacial abnormalities, shortened fingers and toes, and speech and physical developmental delay (Ferreira 2020). SWS is caused by a missense mutation in the COG4 gene, resulting in a G516R residue change. Other pathogenic mutations have been observed in this gene and all are clustered at the C-terminal end of the protein (R724W, R729W, R729A, E764A). These are associated with Congenital Disorder of Glycosylation type 2j (CDGIIj). This is a recessive disease characterized by mild psychomotor delay, mild dysmorphic features, epilepsy, and defective sialylation (Reynders et al. 2009). Besides the mild developmental delay, this disease seems to share virtually no phenotypic similarity with SWS.

Fantz, Douglas et al. (2021) International Worm Meeting "Nfya-1 functions as a substrate of ERK-MAP kinase during Caenorhabditis elegans vulval development"

Krakowiak, Michelle, Frempong, Abena, Powers, Christy, Wilson, Katherine, Fantz, Douglas, Aklilu, Segen

[International Worm Meeting, 2021]

A common bridge between a linear cytoplasmic signal and broad nuclear regulation is the family of MAP kinases which can translocate to the nucleus upon activation by the cytoplasmic signal. One pathway which functions to activate the ERK family of MAP kinases is the Ras signaling pathway which functions at multiple times and locations during the development of Caenorhabditis elegans including the development of the excretory cell, germ cells, male tail, and vulva. It has been most extensively characterized during the development of the vulva which is formed from the vulval precursor cells (VPCs), a set of six equivalent, epithelial cells designated P3.p - P8.p. Although LIN-1 appears to be a primary target of ERK MAP kinase during vulval development, it is likely that other developmentally important molecules are also regulated by ERK-mediated phosphorylation. The identification of physiological substrates of MAP kinases has been aided by the identification of docking site domains in substrate proteins that contribute to high-affinity interactions with kinases. Our laboratory has identified the C. elegans protein, T08D10.1/Nfya-1, as a potential ERK MAP kinase substrate in this manner, and we have initiated a characterization of its role during Ras-mediated development. T08D10.1 possesses significant homology to the CCAAT-box DNA-binding domain of the vertebrate nuclear transcription factor-Y, alpha (NF-YA) family of proteins. NF-Y proteins act as part of a complex to regulate the transcription of a large number of genes, in particular, genes that function in the G1/S cell cycle transition. T08D10.1/Nfya-1 is predicted to code for a protein containing multiple potential phosphorylation sites for ERK MAP kinase and a D-domain docking site. We demonstrate through biochemical analysis of purified Nfya-1 protein that it can act in vitro as a high affinity substrate for activated ERK MAP kinase. We demonstrate through mutant analysis that nfya-1 acts to inhibit vulval development and functions downstream or in parallel to let-60/ras. Mutants also exhibited a low penetrance protruding vulva (Pvul) phenotype. Analysis of gene expression using transgenic animals expressing a GFP reporter indicates potential expression of nfya-1 in the L3 stage VPCs.

Asif, Muhammad Zaka et al. (2021) MicroPubl Biol

Van der Gaag, Victoria L., Edison, Arthur S., Muzio, Cole J., Asif, Muhammad Zaka, Nocilla, Kelsey A., Guo, Jane

[MicroPubl Biol, 2021]

1-Hydroxyphenazine (1-HP) is a small molecule produced by Pseudomonas aeruginosa, a bacterium that is used for pathogenesis models in C. elegans (Cezairliyan et al., 2013; Mahajan-Miklos, Tan, Rahme, & Ausubel, 1999). 1-HP is an especially interesting toxin to study as it has been shown to interact with human cells causing ciliary-slowing associated with dyskinesia and ciliostasis (Wilson et al., 1987). Prior research in our lab has shown that this molecule is toxic to C. elegans, with an LD50 between 150 and 200 M, but C. elegans can glycosylate 1-HP, which detoxifies the molecule (Stupp et al., 2013).

Sambongi Y et al. (1998) European Worm Meeting "Physiological roles of C. elegans copper transport ATPase"

Wakabayashi T, Sambongi Y, Yoshimizu T, Futai M

[European Worm Meeting, 1998]

Copper is essential for cuproenzymes, but its excess causes cell damage through oxidizing proteins and lipids. Therefore, intracellular copper ion concentration must be tightly regulated. Two human genetic disorders, Menkes and Wilson diseases, are defective in copper metabolism. Genes responsible for both disorders encode homologous heavy metal P-type ATPases. To understand the physiological roles of the ATPase, we cloned a homologous cDNA from C. elegans (CUA-1, a 1,238 amino acid protein) that has sequence identities of 46% and 43% to Menkes and Wilson disease proteins, respectively. We showed that the CUA-1 cDNA could rescue the yeast Dccc2 mutant (copper ATPase gene disruptant), suggesting that CUA-1 functions as a copper transporter. The upstream region of cua-1 was fused with the reporter genes (b-galactosidase or GFP) and introduced into the N2 worms. High level expression of the reporter gene was observed specifically in pharyngeal terminal bulb muscle pm6 and most anterior intestinal cells in the transgenic adult worms, suggesting that CUA-1 functions primarily in the digestive organs. In addition to these cells, prominent expression was found in hypodermal cells in larval stages. We also report subcellular localization of CUA-1 and discuss physiological role(s) of this ATPase in C. elegans. We thank Yuji Kohara for providing yk29a9 clone and Andy Fire for GFP and lacZ vectors.

Favello A et al. (1995) Methods Cell Biol "Genomic DNA sequencing methods."

Wilson RK, Hillier L, Favello A

[Methods Cell Biol, 1995]

Sequence analysis of cosmids from C. elegans and other organisms currently is best done using the random or "shotgun" strategy (Wilson et al., 1994). After shearing by sonication, DNA is used to prepare M13 subclone libraries which provide good coverage and high-quality sequence data. The subclones are assembled and the data edited using software tools developed especially for C. elegans genomic sequencing. These same tools facilitate much of the subsequent work to complete both strands of the sequence and resolve any remaining ambiguities. Analysis of the finished sequence is then accomplished using several additional computer tools including Genefinder and ACeDB. Taken together, these methods and tools provide a powerful means for genome analysis in the nematode.

Roubin R et al. (1996) Worm Breeder's Gazette "AN FGF GENE IN THE WORM?"

Thierry-Mieg D, Birnbaum D, Roubin R

[Worm Breeder's Gazette, 1996]

A putative gene coding for a heparin-binding growth factor protein and presenting 30 % similarity with the Fibroblast Growth Factor 5 (FGF5) has been identified on chromosome III of C.elegans (Wilson, R et al, Nature, 1994, 368, 32-38, and Du, Z, unpublished data). The genomic clone CO5D11 carries a complete copy of the gene but no cDNA has yet been identified. In mammals, FGFs are important for embryonic development and have been implicated in some pathologies. Recently, Stern's group has shown that egl-15 encodes a member of the FGF receptor family in C.elegans (DeVore, D. l. et al, Cell, 1995, 83, 611-620). In both C.elegans and D.melanogaster, FGF receptors are involved in cell migration.