Veronica A Marin et al. (2003) International Worm Meeting "Regulation of a GLD-1/POS-1 complex localizes glp-1 mRNA translation in the C. elegans embryo."

Veronica A Marin, Thomas C Evans

[International Worm Meeting, 2003]

In the C. elegans embryo, the Notch receptor GLP-1 is localized to anterior cells by translational regulation of glp-1 mRNA. The mechanisms that mediate this localized translation are not understood. Translational control of glp-1 requires several regulatory elements in the glp-1 3 UTR. In the embryo, a repression element called the GRE is required to repress glp-1 translation in posterior cells. We found that the KH domain protein GLD-1 binds specifically to the glp-1 GRE in vitro and contributes to localized repression of glp-1 in vivo. Furthermore, we found that GLD-1 also binds directly to the Zn-finger protein POS-1, and that the GLD-1/POS-1 complex binds glp-1 RNA with higher affinity than either GLD-1 or POS-1 alone. Both GLD-1 and POS-1 directly contact RNA. As was seen with GLD-1, loss of POS-1 function causes loss of glp-1 mRNA repression in posterior cells of the embryo. GLD-1 is a regulator of multiple mRNAs at different stages of development, while POS-1 is an embryo-specific regulator of posterior cell fates. Both proteins are localized to posterior cells in the embryo. Therefore, these results suggest that POS-1 binding to GLD-1 promotes the specific targeting and repression of glp-1 mRNA in the embryonic posterior. In anterior cells, glp-1 translation also requires inhibition of repression (de-repression) through another element in the glp-1 3 UTR called the GDE. We found that endogenous SPN-4, which is both a POS-1-binding and RNA-binding protein, can be pulled out of embryo extracts by tagged wild type glp-1 RNA but not by RNAs with mutations that extend into the GDE. Loss of SPN-4 function causes loss of GLP-1 expression in the embryo anterior, consistent with SPN-4 functioning as a de-repressor or activator of glp-1 translation. Therefore, the localized translation of glp-1 mRNA may be mediated by two distinct processes; localization of a GLD-1/POS-1 repression complex to posterior cells, and inhibition of residual GLD-1/POS-1 by SPN-4 in anterior cells. The interactions among these RNA-binding proteins help to spatially constrain Notch signaling, which is crucial to the regulation of anterior cell fates. Part of this work was supported by the National Science Foundation, the March of Dimes, and the NIH.

Veronica Marin et al. (2001) International C. elegans Meeting "Identification of factors involved the translational control of GLP-1 in the Caenorhabditis elegans early embryo"

Veronica Marin, Lauren Aveline, Kathyrn Resing, Thomas C Evans, Natalie Ahn

[International C. elegans Meeting, 2001]

GLP-1 is a Notch family receptor that is important in cell fate specification of the early Caenorhabditis elegans embryo. The translation of glp-1 is spatially and temporally regulated through sequences in its 3 untranslated region (UTR). GLP-1 protein is translated mostly in anterior cells beginning at the two-cell stage continuing to the 16-cell stage. Several regulatory regions of glp-1 3 UTR have been identified. There is one region at the 3 end of the UTR that is essential for translational repression in oocytes and 1-cell embryos. This region is called the oocyte control region (OCR). Another region is essential for the special regulation of GLP-1 translation. This GLP-1 localization region (GLR) is both necessary and sufficient for the spatial regulation of GLP-1. The GLR contains both an element necessary for translational repression in posterior cells and another element required for activation of translation in the anterior cells. Our hypothesis is that RNA binding proteins interact with the 3' UTR of glp-1 controlling its translation, and that these proteins contribute to anterior-posterior patterning. In order to identify these proteins, we have performed RNA precipitations to identify proteins that bind the regulatory regions of the glp-1 3 UTR. These RNA precipitations have isolated two bands which can be visualized by UV crosslinking, p58 and p30, that bind with specificity to a region within the GLR that is required for repression of translation in posterior cells. These two bands are not able to crosslink to a probe containing a 5-nucleotide mutation within this repression region. Furthermore, these bands cannot be competed off with an excess of this same mutation. We conclude that p58 and p30 are RNA binding proteins that may be involved in the translational repression of GLP-1 expression in posterior cells. We intend to isolate enough of these polypeptides to identify them using mass spectrometry.

Kim YS et al. (2014) Arch Pharm Res "Protocatechuic acid extends lifespan and increases stress resistance in Caenorhabditis elegans."

Kim YS, Seo HW, Lee MH, Jeon H, Cha DS, Kim DK

[Arch Pharm Res, 2014]

Veronica peregrina has a wide range of types of constituents with various pharmacological properties. Here in this study, we isolated protocatechuic acid (PCA) from V. peregrina and examined PCAs effects on the lifespan and stress tolerance using Caenorhabditis elegans model system. We found that lifespan of wild-type worms was significantly lengthened in the presence of PCA in a dose dependent manner. PCA also elevated tolerance of worms against osmotic, heat shock, and oxidative stress. We also demonstrated antioxidant capacity of PCA by checking intracellular reactive oxygen species level and antioxidant enzyme activities such as catalase and superoxide dismutase. We further investigated several factors including pharyngeal pumping rate and progeny production that might influence prolonged lifespan and enhanced stress tolerance by PCA. Interestingly, both factors were significantly reduced after PCA exposure, indicating PCA exerts longevity activity by shifting food intake and reproduction at least in part. In addition, PCA-treated aged worms showed increased body movement compared to untreated controls suggesting PCA could enhance healthspan as well as lifespan.

Yamazaki, S. et al. (2017) International Worm Meeting "Learning-dependent behavioral modulation of sensory behavior revealed by machine learning and optophysiological analysis in a virtual environment."

Ikejiri, Y., Hiramatsu, F., Yamazaki, S., Fujita, K., Kimura, K., Tanimoto, Y., Hashimoto, K., Maekawa, T., Yamazoe-Umemoto, A.

[International Worm Meeting, 2017]

Animals modify their behavior based on experiences as learning, although identifying component(s) of behavior modulated by learning has been difficult. In contrast to neural activities, which can be monitored in large numbers of cells simultaneously recently, behavior in general is still analyzed in classic ways and insufficiently studied using simple measures, such as velocity, migratory distance, and/or the probability of selecting a particular goal. Comprehensive classifications of animals' behavior by using machine vision and machine learning methods have been achieved (Gomez-Marin et al., Nat Neurosci, 2014; Brown et al., PNAS, 2013). However, these methods have not been applied to animals' sensory behavior because of technical limitations in measuring sensory signals that animals receive during the behavior. To overcome this problem and effectively identify behavioral components modulated by learning, we used machine learning aiming to detect changes in navigation of worms in a measured odor gradient. We have previously reported that, after experiencing the repulsive odor 2-nonanone for 1 h, worm's odor avoidance behavior is enhanced, and that they move away from the odor source more efficiently (Kimura et al., J Neurosci, 2010). We have also quantified the dynamic changes in the odor concentration during odor avoidance behavior (Yamazoe-Umemoto et al., Neurosci Res, 2015). In the present study, we used decision tree, a machine learning algorithm, to extract features of the animal's sensorimotor response during navigation modified by odor learning. During the migration down the odor gradient, naive worms responded to slight increases in the repulsive odor concentration by stopping forward movements and initiating turns. In contrast, the probability of response was lowered after learning, suggesting that the learned worms ignore "a yellow light". Consistently, by calcium imaging of ASH neurons, whose activation causes turns under a virtual odor gradient (Tanimoto et al., this meeting), we found that the ASH response to a small increase in the odor concentration was reduced after learning. Furthermore, by applying the decision tree analysis, multiple mutant strains were categorized into several groups based on behavioral features. Thus, the integrative machine learning analysis of sensory information and behavioral response is a powerful tool to obtain comprehensive understanding of dynamic activities of neural circuits and its modulation by learning.

Quartey MO et al. (2021) Sci Rep "The A(1-38) peptide is a negative regulator of the A(1-42) peptide implicated in Alzheimer disease progression."

Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO

[Sci Rep, 2021]

The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).

Danielle Thierry-Mieg et al. (2003) Worm Breeder's Gazette "www.wormgenes.org , a new gene centered database"

Vahan Simonyan, Michel Potdevin, Mark Sienkiewicz, Yuji KOHARA, Jean Thierry-Mieg, Danielle Thierry-Mieg, Tadasu SHIN-I

[Worm Breeder's Gazette, 2003]

Wormgenes is a new resource for C.elegans offering a detailed summary about each gene and a powerful query system.

Tangrodchanapong T et al. (2020) Front Pharmacol "Frondoside A Attenuates Amyloid- Proteotoxicity in Transgenic Caenorhabditis elegans by Suppressing Its Formation."

Tangrodchanapong T, Sobhon P, Meemon K

[Front Pharmacol, 2020]

Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.

Hodgkin JA (1998) International Journal of Developmental Biology "Seven types of pleiotropy."

Hodgkin JA

[International Journal of Developmental Biology, 1998]

Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.

Tuck S (2011) Curr Biol "Extracellular vesicles: budding regulated by a phosphatidylethanolamine translocase."

Tuck S

[Curr Biol, 2011]

Recent work on a Caenorhabditis elegans transmembrane ATPase reveals a central role for the aminophospholipid phosphatidylethanolamine in the production of a class of extracellular vesicles.

Viney ME et al. (2004) Naturwissenschaften "Is dauer pheromone of Caenorhabditis elegans really a pheromone?"

Viney ME, Franks NR

[Naturwissenschaften, 2004]

Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.