Mondragon A et al. (1998) European Worm Meeting "Characterisation of the C. elegans cadherin superfamily"

Mondragon A, Pettitt J

[European Worm Meeting, 1998]

Cadherins are calcium dependent cell-surface molecules that have been implicated in cell recognition, adhesion, proliferation and morphogenesis both in vertebrates and the fruit fly Drosophila. The C. elegans Genome Sequencing Consortium has reported 10 genes encoding members of the cadherin superfamily, and it is likely that this represents the full complement of cadherins in C. elegans. Two C. elegans cadherins, HMR-1 and CDH-3, have been shown to be required for epithelial cell morphogenesis (1,2), and we would like to determine the roles played by the other cadherins. We are using both RNA interference assays and deletion screens to address this problem. We will present a progress report of this work. The long term aim is to obtain a comprehensive picture of how each cadherin contributes to C. elegans development. It is likely that this work will reveal fundamental aspects of cadherin function that will be applicable to other, more complex, metazoans. 1. Costa et al., (1998). J. Cell Biol. 141, 297-308 2. Pettitt et al., (1996). Development 122 4149-4157.

Mondragon RJ et al. (2018) PLoS One "Multilink communities of multiplex networks."

Iacovacci J, Bianconi G, Mondragon RJ

[PLoS One, 2018]

Multiplex networks describe a large number of complex social, biological and transportation networks where a set of nodes is connected by links of different nature and connotation. Here we uncover the rich community structure of multiplex networks by associating a community to each multilink where the multilinks characterize the connections existing between any two nodes of the multiplex network. Our community detection method reveals the rich interplay between the mesoscale structure of the multiplex networks and their multiplexity. For instance some nodes can belong to many layers and few communities while others can belong to few layers but many communities. Moreover the multilink communities can be formed by a different number of relevant layers. These results point out that mesoscopically there can be large differences in the compressibility of multiplex networks.

Tellez-Arreola JL et al. (2022) J Mol Evol "Analysis of the MCTP Amino Acid Sequence Reveals the Conservation of Putative Calcium- and Lipid-Binding Pockets Within the C2 Domains In Silico."

Estrada-Mondragon A, Lazaro-Guevara JM, Flores-Moran AE, Martinez-Torres A, Tellez-Arreola JL

[J Mol Evol, 2022]

MCTPs (Multiple C2 Domains and Transmembrane region Proteins) are evolutionarily and structurally related to other C2 proteins, which are central to exocytosis and membrane trafficking; however, their specific function has been little studied. MCTPs are associated with endosomes and the endoplasmic reticulum and possess three C2 domains (C2A-C2C) and two transmembrane regions (TMRs) well conserved in different species. Here, we generated structural models of the MCTP C2 domains of C. elegans and analyzed their putative function by docking, which revealed that these domains possess Ca²⁺- and lipid-binding pockets, suggesting that MCTPs play a significant, calcium-dependent role in membrane physiology.

Babbar R et al. (1998) European Worm Meeting "Analysis of the regulatory factors involved in cdh-3 and cdh-9 expression"

Pettitt J, Babbar R

[European Worm Meeting, 1998]

To date, 10 members of the cadherin superfamily have been identified in C. elegans (see abstract by Mondragon and Pettitt). We are interested in understanding the regulation of cadherin expression and to what extent the regulatory mechanisms are conserved between phyla. For reasons outlined below, we are beginning this work by focusing upon the regulation of two cadherin genes, cdh-3 and cdh-9. The upstream region of the cdh-3 gene has been implicated in producing a phenotype termed "Pun" (Pharynx unattatched) when it is present in high copy number transgenes. This phenotype is attributable to the fact that in these animals the connection between the pharynx and the epidermis surrounding the buccal opening fails to from properly and therefore the nematode has effectively no "mouth". The phenotype is lethal, as the nematode is unable to feed. cdh-3 is expressed in the cells responsible for the connection between the pharynx and the epidermis and it seems likely that the Pun phenotype is due to the titration of a trans-acting factor, or factors, by the transgenic cdh-3 promoter sequences. This may provide a means to identify the factor(s) involved. We are attempting to identify the region of the cdh-3 promoter involved by making deletion derivatives of a gfp-based promoter construct and assaying both their expression patterns and whether they confer a Pun phenotype. The C. briggsae orthologue of cdh-9 has been sequenced and the exon structure of the two genes is highly conserved. In addition, regions upstream of the start site and within the first intron are conserved, suggesting that these may represent regulatory elements. The initial goal of this project is to establish the expression pattern of cdh-9, firstly in C. elegans and then in C. briggsae. This will be done by tagging the cdh-9 gene with gfp in a construct and assaying expression in both nematodes. The C. briggsae orthologue will be similarly tagged and analysed. These experiments will have two objectives. Firstly, to confirm the observations made in silico. Secondly, to determine whether any divergence in the expression patterns of this gene in the two nematodes exists, and if so whether this correlates with differences in the cis-acting regulatory sequences.

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.