Matus D et al. (2018) J Dev Biol "G Proteins and GPCRs in C. elegans Development: A Story of Mutual Infidelity."

Promel S, Matus D

[J Dev Biol, 2018]

Many vital processes during C. elegans development, especially the establishment and maintenance of cell polarity in embryogenesis, are controlled by complex signaling pathways. G protein-coupled receptors (GPCRs), such as the four Frizzled family Wnt receptors, are linchpins in regulating and orchestrating several of these mechanisms. However, despite being GPCRs, which usually couple to G proteins, these receptors do not seem to activate classical heterotrimeric G protein-mediated signaling cascades. The view on signaling during embryogenesis is further complicated by the fact that heterotrimeric G proteins do play essential roles in cell polarity during embryogenesis, but their activity is modulated in a predominantly GPCR-independent manner via G protein regulators such as GEFs GAPs and GDIs. Further, the triggered downstream effectors are not typical. Only very few GPCR-dependent and G protein-mediated signaling pathways have been unambiguously defined in this context. This unusual and highly intriguing concept of separating GPCR function and G-protein activity, which is not restricted to embryogenesis in <i>C. elegans</i> but can also be found in other organisms, allows for essential and multi-faceted ways of regulating cellular communication and response. Although its relevance cannot be debated, its impact is still poorly discussed, and <i>C.</i><i>elegans</i> is an ideal model to understand the underlying principles.

Guan K-L et al. (1999) Genes Dev "A G-protein signaling network mediated by an RGS protein."

Han M, Guan K-L

[Genes Dev, 1999]

A wide variety of extracellular stimuli induce signal transduction through receptors coupled to heterotrimeric G proteins, which consist of alpha, beta, and gamma subunits (Gilman 1987). The G alpha subunit has guanine nucleotide binding and GTP hydrolysis activities. Based on function and amino acid sequence homology, the Galpha, G alph i/o, G alpha q, and G alpha 12 (Simon et al. 1991; Hepler and Gilman 1992). As exemplified by the responsiveness of our five senses to environmental stimuli, signaling mediated by trimeric G proteins is often extremely rapid and transient. A key step in achieving such a raid response is the ability of the G alpha subunit to switch between it GDP- and GTP-bound forms. The nucleotide binding state of G alpha is regulated at both the GDP dissociation and GTP hydrolysis steps. Stimulation of receptors by agonists leads to a conformational change in the receptors which can function as a guanine nucleotide exchange factor to stimulate a rapid dissociation of GDP from the inactive G alpha. The nucleotide-free G alpha is then available to bind GTP, leading to the dissociation of G alpha from the G beta gamma heterodimer. Both the G alpha and G beat gamma subunits can interact with and regulate downstream effectors that include adenylyl cyclase, phospholipase C, and ion channels (Gilman 1987; Birnbaumer 1992).

Al-Jawabreh R et al. (2024) Philos Trans R Soc Lond B Biol Sci "Advancing Strongyloides omics data: bridging the gap with Caenorhabditis elegans."

McKenzie D, Suleiman M, Hunt V, Atkinson L, Reynolds K, Lastik D, Al-Jawabreh R, Mousley A

[Philos Trans R Soc Lond B Biol Sci, 2024]

Among nematodes, the free-living model organism <i>Caenorhabditis elegans</i> boasts the most advanced portfolio of high-quality omics data. The resources available for parasitic nematodes, including <i>Strongyloides</i> spp., however, are lagging behind. While <i>C. elegans</i> remains the most tractable nematode and has significantly advanced our understanding of many facets of nematode biology, <i>C. elegans</i> is not suitable as a surrogate system for the study of parasitism and it is important that we improve the omics resources available for parasitic nematode species. Here, we review the omics data available for <i>Strongyloides</i> spp<i>.</i> and compare the available resources to those for <i>C. elegans</i> and other parasitic nematodes. The advancements in <i>C. elegans</i> omics offer a blueprint for improving omics-led research in <i>Strongyloides</i>. We suggest areas of priority for future research that will pave the way for expansions in omics resources and technologies. This article is part of the Theo Murphy meeting issue '<i>Strongyloides</i>: omics to worm-free populations'.

Seegobin SP et al. (2020) Front Neurosci "Progress in LRRK2-Associated Parkinson's Disease Animal Models."

Liang D, Choi I, Blanca Ramirez M, Yue Z, Seegobin SP, Tang B, Heaton GR

[Front Neurosci, 2020]

Mutations in the leucine-rich repeat kinase 2 (<i>LRRK2</i>) gene are the most frequent cause of familial Parkinson's disease (PD). Several genetic manipulations of the <i>LRRK2</i> gene have been developed in animal models such as rodents, <i>Drosophila</i>, <i>Caenorhabditis elegans</i>, and zebrafish. These models can help us further understand the biological function and derive potential pathological mechanisms for LRRK2. Here we discuss common phenotypic themes found in <i>LRRK2</i>-associated PD animal models, highlight several issues that should be addressed in future models, and discuss emerging areas to guide their future development.

L Singulani J et al. (2018) J Fungi (Basel) "Applications of Invertebrate Animal Models to Dimorphic Fungal Infections."

A Assato P, C de Oliveira H, Scorzoni L, M Marcos C, Fusco-Almeida AM, S Mendes-Giannini MJ, L Singulani J

[J Fungi (Basel), 2018]

Dimorphic fungi can be found in the yeast form during infection and as hyphae in the environment and are responsible for a large number of infections worldwide. Invertebrate animals have been shown to be convenient models in the study of fungal infections. These models have the advantages of being low cost, have no ethical issues, and an ease of experimentation, time-efficiency, and the possibility of using a large number of animals per experiment compared to mammalian models. Invertebrate animal models such as <i>Galleria mellonella</i>, <i>Caenorhabditis elegans</i>, and <i>Acanthamoeba</i><i>castellanii</i> have been used to study dimorphic fungal infections in the context of virulence, innate immune response, and the efficacy and toxicity of antifungal agents. In this review, we first summarize the features of these models. In this aspect, the growth temperature, genome sequence, availability of different strains, and body characteristics should be considered in the model choice. Finally, we discuss the contribution and advances of these models, with respect to dimorphic fungi <i>Paracoccidioides</i> spp., <i>Histoplasma capsulatum</i>, <i>Blastomyces dermatitidis</i>, <i>Sporothrix</i> spp., and <i>Talaromyces marneffei (Penicillium marneffei)</i>.

Merrin J (2019) Bioengineering (Basel) "Frontiers in Microfluidics, a Teaching Resource Review."

Merrin J

[Bioengineering (Basel), 2019]

This is a literature teaching resource review for biologically inspired microfluidics courses or exploring the diverse applications of microfluidics. The structure is around key papers and model organisms. While courses gradually change over time, a focus remains on understanding how microfluidics has developed as well as what it can and cannot do for researchers. As a primary starting point, we cover micro-fluid mechanics principles and microfabrication of devices. A variety of applications are discussed using model prokaryotic and eukaryotic organisms from the set of bacteria (<i>Escherichia coli</i>), trypanosomes (<i>Trypanosoma brucei</i>), yeast (<i>Saccharomyces cerevisiae</i>), slime molds (<i>Physarum polycephalum</i>), worms (<i>Caenorhabditis elegans</i>), flies (<i>Drosophila melangoster</i>), plants (<i>Arabidopsis thaliana</i>), and mouse immune cells (<i>Mus musculus</i>). Other engineering and biochemical methods discussed include biomimetics, organ on a chip, inkjet, droplet microfluidics, biotic games, and diagnostics. While we have not yet reached the end-all lab on a chip, microfluidics can still be used effectively for specific applications.

Topf U et al. (2019) Front Neurosci "Ancient Function of Teneurins in Tissue Organization and Neuronal Guidance in the Nematode Caenorhabditis elegans."

Drabikowski K, Topf U

[Front Neurosci, 2019]

The nematode <i>Caenorhabditis elegans</i> expresses the <i>ten-1</i> gene that encodes teneurin. TEN-1 protein is expressed throughout the life of <i>C. elegans</i>. The loss of <i>ten-1</i> function results in embryonic and larval lethality, highlighting its importance for fundamental processes during development. TEN-1 is expressed in the epidermis and neurons. Defects in neuronal pathfinding and epidermal closure are characteristic of <i>ten-1</i> loss-of-function mutations. The molecular mechanisms of TEN-1 function in neurite outgrowth, neuronal pathfinding, and dendritic morphology in <i>C. elegans</i> are largely unknown. Its genetic redundancy with the extracellular matrix receptors integrin and dystroglycan and genetic interactions with several basement membrane components suggest a role for TEN-1 in the maintenance of basement membrane integrity, which is essential for neuronal guidance. Identification of the <i>lat-1</i> gene in <i>C. elegans</i>, which encodes latrophilin, as an interaction partner of <i>ten-1</i> provides further mechanistic insights into TEN-1 function in neuronal development. However, receptor-ligand interactions between LAT-1 and TEN-1 remain to be experimentally proven. The present review discusses the function of teneurin in <i>C. elegans</i>, with a focus on its involvement in the formation of receptor signaling complexes and neuronal networks.

Carol Bastiani et al. (2006) WormBook "Heterotrimeric G proteins in C. elegans."

Jane Mendel, Carol Bastiani

[WormBook, 2006]

Heterotrimeric G proteins, composed of alpha , beta , and gamma subunits, are able to transduce signals from membrane receptors to a wide variety of intracellular effectors. In this role, G proteins effectively function as dimers since the signal is communicated either by the G alpha subunit or the stable G betagamma complex. When inactive, G alpha -GDP associates with G betagamma and the cytoplasmic portion of the receptor. Ligand activation of the receptor stimulates an exchange of GTP for GDP resulting in the active signaling molecules G alpha -GTP and free G betagamma , either of which can interact with effectors. Hydrolysis of GTP restores G alpha -GDP, which then reassociates with G betagamma and receptor to terminate signaling. The rate of G protein activation can be enhanced by the guanine-nucleotide exchange factor, RIC-8 , while the rate of GTP hydrolysis can be enhanced by RGS proteins such as EGL-10 and EAT-16 . Evidence for a receptor-independent G-protein-signaling pathway has been demonstrated in C. elegans early embryogenesis. In this pathway, the G alpha subunits GOA-1 and GPA-16 are apparently activated by the non-transmembrane proteins GPR-1 , GPR-2 , and RIC-8 , and negatively regulated by RGS-7 . The C. elegans genome encodes 21 G alpha , 2 G beta and 2 G gamma subunits. The alpha subunits include one ortholog of each mammalian G alpha family: GSA-1 (Gs), GOA-1 (Gi/o), EGL-30 (Gq) and GPA-12 (G12). The remaining C. elegans alpha subunits ( GPA-1 , GPA-2 , GPA-3 , GPA-4 , GPA-5 , GPA-6 , GPA-7 , GPA-8 , GPA-9 , GPA-10 , GPA-11 , GPA-13 , GPA-14 , GPA-15 , GPA-16 , GPA-17 and ODR-3 ) are most similar to the Gi/o family, but do not share sufficient homology to allow classification. The conserved G alpha subunits, with the exception of GPA-12 , are expressed broadly while 14 of the new G alpha genes are expressed in subsets of chemosensory neurons. Consistent with their expression patterns, the conserved C. elegans alpha subunits, GSA-1 , GOA-1 and EGL-30 are involved in diverse and fundamental aspects of development and behavior. GOA-1 acts redundantly with GPA-16 in positioning of the mitotic spindle in early embryos. EGL-30 and GSA-1 are required for viability starting from the first larval stage. In addition to their roles in development and behaviors such as egg laying and locomotion, the EGL-30 , GSA-1 and GOA-1 pathways interact in a network to regulate acetylcholine release by the ventral cord motor neurons. EGL-30 provides the core signals for vesicle release, GOA-1 negatively regulates the EGL-30 pathway, and GSA-1 modulates this pathway, perhaps by providing positional cues. Constitutively activated GPA-12 affects pharyngeal pumping. The G alpha subunits unique to C. elegans are primarily involved in chemosensation. The G beta subunit, GPB-1 , as well as the G gamma subunit, GPC-2 , appear to function along with the alpha subunits in the classic G protein heterotrimer. The remaining G beta subunit, GPB-2 , is thought to regulate the function of certain RGS proteins, while the remaining G gamma subunit, GPC-1 , has a restricted role in chemosensation. The functional difference for most G protein pathways in C. elegans, therefore, resides in the alpha subunit. Many cells in C. elegans express multiple G alpha subunits, and multiple G protein pathways are known to function in specific cell types. For example, Go, Gq and Gs-mediated signaling occurs in the ventral cord motor neurons. Similarly, certain amphid neurons use multiple G protein pathways to both positively and negatively regulate chemosensation. C. elegans thus provides a powerful model for the study of interactions between and regulation of G protein signaling.

Torres M et al. (2020) J Fungi (Basel) "In Vitro or In Vivo Models, the Next Frontier for Unraveling Interactions between Malassezia spp. and Hosts. How Much Do We Know?"

Celis Ramirez AM, Torres M, de Cock H

[J Fungi (Basel), 2020]

<i>Malassezia</i> is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated with the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interactions of <i>Malassezia</i> spp., and unraveling this implies the implementation of infection models. In this mini review, we present different models that have been implemented in fungal infections studies with greater attention to <i>Malassezia</i> spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have been shown to have reliable results, which correlate with those obtained from mammalian models. Examples of alternative models are <i>Caenorhabditis elegans</i>, <i>Drosophila melanogaster</i>, <i>Tenebrio molitor</i>, and <i>Galleria mellonella</i>. These are invertebrates that have been implemented in the study of <i>Malassezia</i> spp. infections in order to identify differences in virulence between <i>Malassezia</i> species.

Yue Y et al. (2021) Curr Res Food Sci "Caenorhabditis elegans as a model for obesity research."

Park Y, Yue Y, Li S, Shen P

[Curr Res Food Sci, 2021]

<i>Caenorhabditis elegans</i>, a free-living nematode, is an animal model that has been extensively employed in a variety of research fields, including in the study of obesity. Its favorable features include its compact size, short life cycle, large brood size, easy handling, low cost, availability of complete genetic information, 65% conserved human diseases-associated genes, relatively easy genetic manipulation, and research using <i>Caenorhabditis elegans</i> does not require approvals by the Institutional Animal Care and Use Committee. These advantages make <i>Caenorhabditis elegans</i> a great <i>in vivo</i> model for life science research including obesity research. In this review, we provide graphic overviews of <i>Caenorhabditis elegans'</i> basic anatomy, growth conditions, routes of compound delivery, and fat metabolism, both synthesis and degradation pathways, including major signaling pathways involved. Our aim is to provide an overview for researchers interested in applying <i>C. elegans</i> as an <i>in vivo</i> model for the screening and identification of anti-obesity bioactive compounds prior to testing in vertebrate animal models.