Castillo-Quan JI et al. (2016) Cell "Metformin: Restraining Nucleocytoplasmic Shuttling to Fight Cancer and Aging."

Blackwell TK, Castillo-Quan JI

[Cell, 2016]

In this issue of Cell, Wu etal. employed C.elegans and human cell experiments to identify a pathway through which metformin increases lifespan and inhibits growth. A key transcriptional target, ACAD10, is activated when metformin induces nuclear exclusion of the GTPase RagC, thereby inhibiting mTORC1 through an unexpected mechanism.

Brissette B et al. (2019) Neuron "Insulin-like Peptides as Agents of Social Change."

Ringstad N, Brissette B

[Neuron, 2019]

Many behaviors promote reproduction or food finding. These critical functions of behavior can conflict; successful reproductive strategies can grow populations to the point where food is depleted. In this issue of Neuron, Wu etal. (2019) show how the nematode C.elegans detects crowding to change feeding behavior by coupling pheromone sensing to signaling via insulin-like peptides.

Wu D et al. (1997) Science "Interaction and regulation of subcellular localization of CED-4 by CED-9."

Wu D, Nunez G, Wallen HD

[Science, 1997]

The Caenorhabditis elegans survival gene ced-9 regulates ced-4 activity and inhibits cell death, but the mechanism by which this occurs is unknown. Through a genetic screen for CED-4-binding proteins, CED-9 was identified as an interacting partner of CED-4. CED-9, but not loss-of-function mutants, associated specifically with CED-4 in yeast or mammalian cells. The CED-9 protein localized primarily to intracellular membranes and the perinuclear region, whereas CED-4 was distributed in the cytosol. Expression of CED-9, but not a mutant lacking the carboxy-terminal hydrophobic domain, targeted CED-4 from the cytosol to intracellular membranes in mammalian cells. Thus, the actions of CED-4 and CED-9 are directly linked, which could provide the basis for the regulation of programmed cell death in C. elegans.AD - Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.FAU - Wu, DAU - Wu DFAU - Wallen, H DAU - Wallen HDFAU - Nunez, GAU - Nunez GLA - engID - CA-64556/CA/NCIID - T32A107413-03/PHSPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Calcium-Binding Proteins)RN - 0 (Ced-4 protein)RN - 0 (Ced-9 protein)RN - 0 (Helminth Proteins)RN - 0 (Proto-Oncogene Proteins)RN - 0 (bcl-x protein)SB - IM

Tuli MA et al. (2018) WormBook "Caenorhabditis nomenclature."

Tuli MA, Daul A, Schedl T

[WormBook, 2018]

Genetic nomenclature for Caenorhabditis species and other nematodes is supervised by WormBase in collaboration with the Caenorhabditis Genetics Center (CGC) and with essential input from the community of scientists working on C. elegans and other nematodes.

Lüders J (2023) Curr Biol "Microtubule cytoskeleton: The centrosome gains a membrane."

Lü\;ders J

[Curr Biol, 2023]

Identification of a membrane structure, termed the 'centriculum', in Caenorhabditis elegans embryos challenges the textbook view of the centrosome - a major microtubule organizing center in animal cells - as an organelle that lacks a surrounding membrane.

Kimura K et al. (2011) Bioarchitecture "A novel mechanism of microtubule length-dependent force to pull centrosomes toward the cell center."

Kimura A, Kimura K

[Bioarchitecture, 2011]

The centrosome is a major microtubule-organizing center in animal cells, and its intracellular positioning is critical for defining intracellular architecture. The centrosome positions itself at the cell center. Centrosome centration depends on the microtubule cytoskeleton. To accomplish robust centration regardless of the cell size or cell shape, it has been assumed that the force mediated by the microtubules depends on microtubule length. However, a concrete mechanism to generate forces to pull the centrosome in a microtubule length-dependent manner has been elusive. Recently, we successfully demonstrated that centrosome-directed movement of intracellular organelles along microtubules drives centrosome centration in the Caenorhabditis elegans early embryo. Based on this observation, we proposed the centrosome-organelle mutual pulling model in which the reaction forces of organelle transport generated along microtubules act as a driving force that pulls the centrosomes toward the cell center. This is the first experiment-based model that accounts for the microtubule length-dependent pulling force generated in the cytoplasm contributing to centrosome centration. Intriguingly, this model is consistent with a recent estimation that the pulling force is proportional to the cubic length of microtubules.

Lascarez-Lagunas LI et al. (2023) PLoS Genet "Chromatin landscape, DSB levels, and cKU-70/80 contribute to patterning of meiotic DSB processing along chromosomes in C. elegans."

Lascarez-Lagunas LI, Colaiacovo MP, Nadarajan S, Berson E, Diaz-Pacheco BN, Martinez-Garcia M

[PLoS Genet, 2023]

Programmed DNA double-strand break (DSB) formation is essential for achieving accurate chromosome segregation during meiosis. DSB repair timing and template choice are tightly regulated. However, little is known about how DSB distribution and the choice of repair pathway are regulated along the length of chromosomes, which has direct effects on the recombination landscape and chromosome remodeling at late prophase I. Here, we use the spatiotemporal resolution of meiosis in the Caenorhabditis elegans germline along with genetic approaches to study distribution of DSB processing and its regulation. High-resolution imaging of computationally straightened chromosomes immunostained for the RAD-51 recombinase marking DSB repair sites reveals that the pattern of RAD-51 foci throughout pachytene resembles crossover distribution in wild type. Specifically, RAD-51 foci occur primarily along the gene-poor distal thirds of the chromosomes in both early and late pachytene, and on both the X and the autosomes. However, this biased off-center distribution can be abrogated by the formation of excess DSBs. Reduced condensin function, but not an increase in total physical axial length, results in a homogeneous distribution of RAD-51 foci, whereas regulation of H3K9 methylation is required for the enrichment of RAD-51 at off-center positions. Finally, the DSB recognition heterodimer cKU-70/80, but not the non-homologous end-joining canonical ligase LIG-4, contributes to the enriched off-center distribution of RAD-51 foci. Taken together, our data supports a model by which regulation of the chromatin landscape, DSB levels, and DSB detection by cKU-70/80 collaborate to promote DSB processing by homologous recombination at off-center regions of the chromosomes in C. elegans.

Wu Y et al. (2010) Neurobiol Aging "Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers."

Cao Z, Wu Y, Luo Y, Klein WL

[Neurobiol Aging, 2010]

Heat shock response, mediated by heat shock proteins, is a highly conserved physiological process in multicellular organisms for reestablishment of cellular homeostasis. Expression of heat shock factors and subsequent heat shock protein plays a role in protection against proteotoxicity in invertebrate and vertebrate models. Proteotoxicity due to beta-amyloid peptide (Abeta) oligomerization has been linked to the pathogenesis of Alzheimer's disease. Previously, we demonstrated that progressive paralysis induced by expression of human Abeta(1-42) in transgenic Caenorhabditis elegans was alleviated by Abeta oligomer inhibitors Ginkgo biloba extract and its constituents [Wu, Y., Wu, Z., Butko, P., Christen, Y., Lambert, M.P., Klein, W.L., Link, C.D., Luo, Y., 2006. Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans. J. Neurosci. 26(50): 13102-13113]. In this study, we apply a protective heat shock to the transgenic C. elegans and demonstrate: (1) a delay in paralysis, (2) increased expression of small heat shock protein HSP16.2, and (3) significant reduction of Abeta oligomers in a heat shock time-dependent manner. These results suggest that transient heat shock lessens Abeta toxicity by diminishing Abeta oligomerization, which provides a link between up regulation of endogenous chaperone proteins and protection against Abeta proteotoxicity in vivo.

Jones CA et al. (1996) Photochem Photobiol "Replication in UV-irradiated Caenorhabditis elegans embryos."

Hartman PS, Jones CA

[Photochem Photobiol, 1996]

Replication continues in wild-type (but not rad mutant) Caenorhabditis elegans embryos even after exposure to massive fluences of UV radiation. It is of interest to elucidate the mechanism(s) for this ''damage-resistant'' DNA synthesis. In this study, DNA from unirradiated and UV-irradiated wild-type embryos was examined using the electron microscope. Large fluences of UV radiation (180 J m(-2)) had little effect on either replication bubble size or distances between bubbles in wild-type embryos, indicating that the damage-resistant DNA synthesis was not grossly aberrant. Conversely, UV irradiation significantly decreased center-to-center distances between bubbles in excision-repair-deficient rad-3 embryos. This suggests that the decreased DNA synthesis observed after UV irradiation in rad-3 embryos is due largely to blockage of elongation of DNA synthesis.

Martin J et al. (2009) Nucleic Acids Res "Nematode.net update 2008: improvements enabling more efficient data mining and comparative nematode genomics."

Martin J, Mitreva M, Wylie T, Wang Z, Abubucker S, Yin Y

[Nucleic Acids Res, 2009]

Nematode.net (http://nematode.net) is a publicly available resource dedicated to the study of parasitic nematodes. In 2000, the Genome Center at Washington University (GC) joined a consortium including the Nematode Genomics group in Edinburgh, and the Pathogen Sequencing Unit of the Sanger Institute to generate expressed sequence tags (ESTs) as an inexpensive and efficient solution for gene discovery in parasitic nematodes. As of 2008 the GC, sampling key parasites of humans, animals and plants, has generated over 500 000 ESTs and 1.2 million genome survey sequences from more than 30 non-Caenorhabditis elegans nematodes. Nematode.net was implemented to offer user-friendly access to data produced by this project. In addition to sequence data, the site hosts: assembled NemaGene clusters in GBrowse views characterizing composition and protein homology, functional Gene Ontology annotations presented via the AmiGO browser, KEGG-based graphical display of NemaGene clusters mapped to metabolic pathways, codon usage tables, NemFam protein families which represent conserved nematode-restricted coding sequences not found in public protein databases, a web-based WU-BLAST search tool that allows complex querying and other assorted resources. The primary aim of Nematode.net is the dissemination of this diverse collection of information to the broader scientific community in a way that is useful, consistent, centralized and enduring.