O''Neil, RG et al. (2005) Pflugers Arch - European Journal of Physiology "The mechanosensitive nature of TRPV channels."

Heller, S, O''Neil, RG

[Pflugers Arch - European Journal of Physiology, 2005]

Transient receptor potential vanilloid (TRPV) channels are widely expressed in both sensory and nonsensory cells. Whereas the channels display a broad diversity to activation by chemical and physical stimuli, activation by mechanical stimuli is common to many members of this group in both lower and higher organisms. Genetic screening in Caenorhabditis elegans has demonstrated an essential role for two TRPV channels in sensory neurons. OSM-9 and OCR-2, for example, are essential for both osmosensory and mechanosensory (nose-touch) behaviors. Likewise, two Drosophila TRPV channels, NAN and IAV, have been shown to be critical for hearing by the mechanosensitive chordotonal organs located in the fly''''s antennae. The mechanosensitive nature of the channels appears to be conserved in higher organisms for some TRPV channels. Two vertebrate channels, TRPV2 and TRPV4, are sensitive to hypotonic cell swelling, shear stress/fluid flow (TRPV4), and membrane stretch (TRPV2). In the osmosensing neurons of the hypothalamus (circumventricular organs), TRPV4 appears to function as an osmoreceptor, or part of an osmoreceptor complex, in control of vasopressin release, whereas in inner ear hair cells and vascular baroreceptors a mechanosensory role is suggestive, but not demonstrated. Finally, in many nonsensory cells expressing TRPV4, such as vascular endothelial cells and renal tubular epithelial cells, the channel exhibits well-developed local mechanosensory transduction processes where both cell swelling and shear stress/fluid flow lead to channel activation. Hence, many TRPV channels, or combinations of TRPV channels, display a mechanosensitive nature that underlies multiple mechanosensitive processes from worms to mammals.

Spaulding EL et al. (2022) Nat Commun "RG/RGG repeats in the C. elegans homologs of Nucleolin and GAR1 contribute to sub-nucleolar phase separation."

Updike DL, Spaulding EL, Feidler AM, Cook LA

[Nat Commun, 2022]

The intrinsically disordered RG/RGG repeat domain is found in several nucleolar and P-granule proteins, but how it influences their phase separation into biomolecular condensates is unclear. We survey all RG/RGG repeats in C. elegans and uncover nucleolar and P-granule-specific RG/RGG motifs. An uncharacterized protein, K07H8.10, contains the longest nucleolar-like RG/RGG domain in C. elegans. Domain and sequence similarity, as well as nucleolar localization, reveals K07H8.10 (NUCL-1) to be the homolog of Nucleolin, a protein conserved across animals, plants, and fungi, but previously thought to be absent in nematodes. Deleting the RG/RGG repeats within endogenous NUCL-1 and a second nucleolar protein, GARR-1 (GAR1), demonstrates these domains are dispensable for nucleolar accumulation. Instead, their RG/RGG repeats contribute to the phase separation of proteins into nucleolar sub-compartments. Despite this common RG/RGG repeat function, only removal of the GARR-1 RG/RGG domain affects worm fertility and development, decoupling precise sub-nucleolar structure from nucleolar function.

Wang J et al. (2023) Carbohydr Polym "A ginseng-derived rhamnogalacturonan I (RG-I) pectin promotes longevity via TOR signalling in Caenorhabditis elegans."

Wang Y, Li X, Yu Y, Xue D, Wang J, Zhou Y

[Carbohydr Polym, 2023]

Panax ginseng C. A. Meyer (ginseng), a traditional Chinese herb, is usually used to improve health and increase anti-aging activity for human. Polysaccharides are bioactive components of ginseng. Herein, using Caenorhabditis elegans as a model, we discovered a ginseng-derived rhamnogalacturonan I (RG-I) pectin WGPA-1-RG promoted longevity via TOR signalling pathway with transcription factors FOXO/DAF-16 and Nrf2/SKN-1 accumulated in the nucleus, where they activated target genes. And the WGPA-1-RG-mediated lifespan extension was dependent on endocytosis, rather than a bacterial metabolic process. Glycosidic linkage analyses combined with arabinose- and galactose-releasing enzyme hydrolyses identified the RG-I backbone of WGPA-1-RG was primarily substituted with α-1,5-linked arabinan, β-1,4-linked galactan and arabinogalactan II (AG-II) side chains. Feeding worms with the WGPA-1-RG-derived fractions which lost distinct structural elements by enzymatic digestions, we found the arabinan side chains prominently contributed to the longevity-promoting activity of WGPA-1-RG. These findings provide a novel ginseng-derived nutrient that potentially increases human longevity.

Franz M et al. (1987) Parasitol Res "Electron-microscopic observations on the female worms of six Onchocerca species from cattle and red deer."

Copeman DB, Franz M, Schulz-Key H

[Parasitol Res, 1987]

The midbody regions of female worms of six Onchocerca species (O. flexuosa, O. tarsicola, O. lienalis, O. gutturosa, O. armillata, O. gibsoni) were studied by transmission electron microscopy. The cuticular layering was rather similar in all species with the ridges built up by the cortical layers and the inner cuticular striations by the median or basal layers. Differences in the epicuticular morphology were considerable. O. flexuosa and O. lienalis had a thin epicuticle without protuberances, the epicuticle of O. armillata carried small knobs, and O. tarsicola, O. gutturosa, and O. gibsoni had a thick trilaminar epicuticle with long protuberances. Extreme hypertrophy of hypodermis and reductions of somatic musculature were observed in O. flexuosa and O. gibsoni. Less extended thickenings of the hypodermis were observed in the other species. No degenerative alterations were found in the muscle cells of O. gutturosa and O. lienalis. The intestinal lumen of most of the species was in a central position, but in O. tarsicola and O. gibsoni the lumen was reduced to small clefts between the intestinal cells. In these species, numerous electron-dense, concentric granules were observed in the cytoplasm of the intestinal cells. The proportions of the various organs differed considerably from species to species, e.g., the uteri contained the embryos filed one behind the other in O. tarsicola, whereas 50 or more embryos were found beside one another in cross-sections of the uterus of O. gibsoni. The comparative study showed that O. gibsoni and O. volvulus have many derived morphological characteristics in common and that in the other species more primitive stages of development of these morphological marks can be observed.

Zhang S et al. (2021) Environ Pollut "Responses of Caenorhabditis elegans to various surface modifications of alumina nanoparticles"

Zhang Z, Xu Y, Mao X, Chu Q, Zhang S, Zhang M

[Environ Pollut, 2021]

The surface modifications of nanoparticles (NPs), are well-recognized parameters that affect the toxicity, while there has no study on toxicity of Al(2)O(3) NPs with different surface modification. Therefore, for the first time, this study pays attention to evaluating the toxicity and potential mechanism of pristine Al(2)O(3) NPs (p-Al(2)O(3)), hydrophilic (w-Al(2)O(3)) and lipophilic (o-Al(2)O(3)) modifications of Al(2)O(3) NPs both in vitro and in vivo. Applied concentrations of 10, 20, 40, 80,100 and 200 μg/mL for 24 h exposure on Caenorhabditis elegans (C. elegans), while 100 μg/mL of Al(2)O(3) NPs significantly decreased the survival rate. Using multiple toxicological endpoints, we found that o-Al(2)O(3) NPs (100 μg/mL) could induce more severe toxicity than p-Al(2)O(3) and w-Al(2)O(3) NPs. After uptake by C. elegans, o-Al(2)O(3) NPs increased the intestinal permeability, easily swallow and further destroy the intestinal membrane cells. Besides, cytotoxicity evaluation revealed that o-Al(2)O(3) NPs (100 μg/mL) are more toxic than p-Al(2)O(3) and w-Al(2)O(3). Once inside the cell, o-Al(2)O(3) NPs could attack mitochondria and induce the over-production of reactive oxygen species (ROS), which destroy the intracellular redox balance and lead to apoptosis. Furthermore, the transcriptome sequencing and RT-qPCR data also demonstrated that the toxicity of o-Al(2)O(3) NPs is highly related to the damage of cell membrane and the imbalance of intracellular redox. Generally, our study has offered a comprehensive sight to the adverse effects of different surface modifications of Al(2)O(3) NPs on environmental organisms and the possible underlying mechanisms.

Bain O et al. Ann Parasitol Hum Comp "[Redescription of Onchocerca gibsoni C. et J., 1910 (author's transl)]."

Bain O, Beveridge I

[Ann Parasitol Hum Comp]

O. gibsoni is redescribed; the hypoderma and the musculature of the female body are studied on transversal sections and compared to several other species of Onchocerca. These structures and the general morphology show the autonomy of a small line of asiatic and african Onchocerca of Bovines (O. gibsoni, O. dukei, O. ochengi and, probably, the other nodular Onchocerca of Bovinae), to which the human parasite, O. volvulus, belongs. The presence of O. gibsoni in Africa is doubtful.

Spaulding, Emily et al. (2021) International Worm Meeting "The C. elegans homolog of Nucleolin, NUCL-1, contributes to nucleolar organization through its intrinsically disordered RG/RGG repeat domain"

Updike, Dustin, Spaulding, Emily, Feidler, Alexis

[International Worm Meeting, 2021]

Intrinsically disordered domains are found in 30-40% of human proteins, many of which undergo liquid-liquid phase separation (LLPS). How these domains influence LLPS-mediated membraneless organelle (MLO) formation and organization in vivo is unclear. One such domain, consisting of Arginine and Glycine (RG/RGG) repeats, is critical for both P-granule and nucleolar function in C. elegans. We have identified 551 proteins with 3 or more regularly spaced RG/RGG repeats in C. elegans. Gene Ontology analysis reveals that these RG/RGG repeat-containing proteins are enriched in MLOs, including the nucleolus and P-granules. MEME motif discovery was used to identify a phenylalanine-rich RG/RGG motif typical of nucleolar proteins and a tyrosine-rich RG/RGG motif typical of P-granule proteins. These motifs were then used to predict the MLO localization of a highly abundant but uncharacterized protein, K07H8.10. The 176 amino acid-long RG/RGG repeat domain of K07H8.10 is the longest in C. elegans and is interspersed with phenylalanine, predicting nucleolar localization. In addition to its N terminal RG/RGG repeat domain, K07H8.10 contains a coiled-coil acidic domain and two C terminal RNA recognition motifs. Both the HHpred and the MARRVEL bioinformatics toolkits predict homology to Nucleolin, which contains these same three domains, although configured in a different arrangement in nematodes. We have fluorescently tagged K07H8.10 (now named NUCL-1) in the C. elegans germline and confirmed its nucleolar localization. Deleting the N terminal RG/RGG repeat domain of NUCL-1 results in fertile worms and does not impair NUCL-1 localization to the nucleolus. However, super resolution imaging of NUCL-1 in living worms reveals that sub-nucleolar compartmentalization of both NUCL-1 and Fibrillarin (FIB-1) are disrupted. Our results indicate that the NUCL-1 RG/RGG repeat domain is dispensable for localization to the nucleolus but is crucial for overall nucleolar organization.

Wang P et al. (2012) Proc Natl Acad Sci U S A "O-GlcNAc cycling mutants modulate proteotoxicity in Caenorhabditis elegans models of human neurodegenerative diseases."

Love DC, Wang P, Hanover JA, Krause MW, Lazarus BD, Forsythe ME

[Proc Natl Acad Sci U S A, 2012]

O-GlcNAcylation is an abundant posttranslational modification in the brain implicated in human neurodegenerative diseases. We have exploited viable null alleles of the enzymes of O-GlcNAc cycling to examine the role of O-GlcNAcylation in well-characterized Caenorhabditis elegans models of neurodegenerative proteotoxicity. O-GlcNAc cycling dramatically modulated the severity of the phenotype in transgenic models of tauopathy, amyloid -peptide, and polyglutamine expansion. Intriguingly, loss of function of O-GlcNAc transferase alleviated, whereas loss of O-GlcNAcase enhanced, the phenotype of multiple neurodegenerative disease models. The O-GlcNAc cycling mutants act in part by altering DAF-16-dependent transcription and modulating the protein degradation machinery. These findings suggest that O-GlcNAc levels may directly influence neurodegenerative disease progression, thus making the enzymes of O-GlcNAc cycling attractive targets for neurodegenerative disease therapies.

Cheung BHH et al. (2005) Curr Biol "Experience-dependent modulation of C. elegans behavior by ambient oxygen."

Cohen M, Rogers C, Cheung BHH, De Bono M, Albayram O

[Curr Biol, 2005]

Background: Ambient oxygen (O(2)) influences the behavior of organisms from bacteria to man. In C. elegans, an atypical O(2) binding soluble guanylate cyclase (sGC), GCY-35, regulates O(2) responses. However, how acute and chronic changes in O(2) modify behavior is poorly understood. Results: Aggregating C. elegans strains can respond to a reduction in ambient O(2) by a rapid, reversible, and graded inhibition of roaming behavior. This aerokinetic response is mediated by GCY-35 and GCY-36 sGCs, which appear to become activated as O(2) levels drop and to depolarize the AQR, PQR, and URX neurons. Coexpression of GCY-35 and GCY-36 is sufficient to transform olfactory neurons into O(2) sensors. Natural variation at the npr-1 neuropeptide receptor alters both food-sensing and O(2)-sensing circuits to reconfigure the salient features of the C. elegans environment. When cultivated in 1% O(2) for a few hours, C. elegans reset their preferred ambient O(2), seeking instead of avoiding 0%-5% O(2). This plasticity involves reprogramming the AQR, PQR, and URX neurons. Conclusions: To navigate O(2) gradients, C. elegans can modulate turning rates and speed of movement. Aerotaxis can be reprogrammed by experience or engineered artificially. We propose a model in which prolonged activation of the AQR, PQR, and URX neurons by low O(2) switches on previously inactive O(2) sensors. This enables aerotaxis to low O(2) environments and may encode a "memory" of previous cultivation in low O(2).

Wells L et al. (2001) Science "Glycosylation of nucleocytoplasmic proteins: signal transduction and O-GlcNAc."

Hart GW, Wells L, Vosseller K

[Science, 2001]

The dynamic glycosylation of serine or threonine residues on nuclear and cytosolic proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) is abundant in all multicellular eukaryotes. On several proteins, O-GlcNAc and O-phosphate alternatively occupy the same or adjacent sites, leading to the hypothesis that one function of this saccharide is to transiently block phosphorylation. The diversity of proteins modified by O-GlcNAc implies its importance in many basic cellular and disease processes. Here we systematically examine the current data implicating O-GlcNAc as a regulatory modification important to signal transduction cascades.