Kipreos ET et al. (2000) Genome Biol "The F-box protein family."

Kipreos ET, Pagano M

[Genome Biol, 2000]

SUMMARY: The F-box is a protein motif of approximately 50 amino acids that functions as a site of protein-protein interaction. F-box proteins were first characterized as components of SCF ubiquitin-ligase complexes (named after their main components, Skp I, Cullin, and an F-box protein), in which they bind substrates for ubiquitin-mediated proteolysis. The F-box motif links the F-box protein to other components of the SCF complex by binding the core SCF component Skp I. F-box proteins have more recently been discovered to function in non-SCF protein complexes in a variety of cellular functions. There are 11 F-box proteins in budding yeast, 326 predicted in Caenorhabditis elegans, 22 in Drosophila, and at least 38 in humans. F-box proteins often include additional carboxy-terminal motifs capable of protein-protein interaction; the most common secondary motifs in yeast and human F-box proteins are WD repeats and leucine-rich repeats, both of which have been found to bind phosphorylated substrates to the SCF complex. The majority of F-box proteins have other associated motifs, and the functions of most of these proteins have not yet been defined.

Veerapathiran S et al. (2018) J Biosci "Fluorescence techniques in developmental biology."

Veerapathiran S, Wohland T

[J Biosci, 2018]

Advanced fluorescence techniques, commonly known as the F-techniques, measure the kinetics and the interactions of biomolecules with high sensitivity and spatiotemporal resolution. Applications of the F-techniques, which were initially limited to cells, were further extended to study in vivo protein organization and dynamics in whole organisms. The integration of F-techniques with multi-photon microscopy and light-sheet microscopy widened their applications in the field of developmental biology. It became possible to penetrate the thick tissues of living organisms and obtain good signal-to-noise ratio with reduced photo-induced toxicity. In this review, we discuss the principle and the applications of the three most commonly used F-techniques in developmental biology: Fluorescence Recovery After Photo-bleaching (FRAP), Fo rster Resonance Energy Transfer (FRET), and Fluorescence Correlation and Cross-Correlation Spectroscopy (FCS and FCCS).

Hodgkin J (2002) Genes Dev "The remarkable ubiquity of DM domain factors as regulators of sexual phenotype: ancestry or aptitude?"

Hodgkin J

[Genes Dev, 2002]

The CM domain is a cysteine-rich DNA-binding motif first recognized in proteins encoded by the Drosophila set determination gene doublesex (Erdman and Burtis 1993; Zhu et al. 2000). As the name doublesex (dsx) suggests, this gene has functions in both sexes: Its transcripts undergo sex-specific alternative splicing, so that it can encode either a male-specific isoform, DSX(M), or a female-specific isoform, DSX(F) (Baker and Wolfner 1988; Burtis and Baker 1989). These proteins have the same N-terminal DNA-binding domain, but different C termini that confer different regulatory properties on the two forms. The expression of DSX(M) directs male development, and the expression of DSX(F) directs female development, throughout most of the somatic tissues of the fruit fly.

Schierenberg E et al. (1992) Seminars in Developmental Biology "The establishment of embryonic axes and determination of cell fates in embryos of the nematode Caenorhabditis elegans."

Schierenberg E, Strome S

[Seminars in Developmental Biology, 1992]

At the 4-cell stage of the C. elegans embryo, three axes can be defined: anterior-posterior (A-P), dorsal-ventral (D-V), and left-right (L-R). The A-P axis first becomes obvious in the newly fertilized 1-cell embryo. Pronouned cytoplasmic assymmetries arise along the A-P axis during the first cell cycle, after which the zygote undergoes a series of stem cell-like cleavages with an A-P orientation of the mitotic spindle; these cleavages generate several somatic founder cells and a primordial germ cell. The D-V and L-R axes are defined by the direction of spindle rotation as the 2-cell embryo divides into four cells. In contrast to the A-P axis, there do not appear to be cellular asymmetries associated with the D-V and L-R axes, and both axes can easily be reversed by micromanipulation. Thus, with respect to the roles that the embryonic axes serve in cell-fate determination in the early C. elegans embryo, it appears that internally transmitted developmental information is differentially segregated along the A-P axis, but not along the D-V or L-R axes. Instead, D-V and L-R differences in the fates of cells within lineages appear to be dictated by differential

Sadeghian F et al. (2022) Life (Basel) "Functional Insights into Protein Kinase A (PKA) Signaling from C. elegans."

Castaneda PG, Sadeghian F, Cram EJ, Amin MR

[Life (Basel), 2022]

Protein kinase A (PKA), which regulates a diverse set of biological functions downstream of cyclic AMP (cAMP), is a tetramer consisting of two catalytic subunits (PKA-C) and two regulatory subunits (PKA-R). When cAMP binds the PKA-R subunits, the PKA-C subunits are released and interact with downstream effectors. In Caenorhabditis elegans (C. elegans), PKA-C and PKA-R are encoded by kin-1 and kin-2, respectively. This review focuses on the contributions of work in C. elegans to our understanding of the many roles of PKA, including contractility and oocyte maturation in the reproductive system, lipid metabolism, physiology, mitochondrial function and lifespan, and a wide variety of behaviors. C. elegans provides a powerful genetic platform for understanding how this kinase can regulate an astounding variety of physiological responses.

Redl M et al. (2024) Planta Med "Application of 3Rs in Caenorhabditis elegans Research for the Identification of Health-Promoting Natural Products."

Redl M, Shayegan A, Rollinger JM

[Planta Med, 2024]

The average age of the population is increasing worldwide, which has a profound impact on our society. This leads to an increasing demand for medicines and requires the development of new strategies to promote health during the additional years. In the search for resources and therapeutics for improved health during an extended life span, attention has to be paid to environmental exposure and ecosystem burdens that inevitably emerge with the extended consumption of medicines and drug development, even in the preclinical stage. The hereby introduced sustainable strategy for drug discovery is built on 3Rs, "R: obustness, R: eliability, and saving R: esources", inspired by both the 3Rs used in animal experiments and environmental protection, and centers on the usefulness and the variety of the small model organism <i>Caenorhabditis elegans</i> for detecting health-promoting natural products. A workflow encompassing a multilevel screening approach is presented to maximize the amount of information on health-promoting samples, while considering the 3Rs. A detailed, methodology- and praxis-oriented compilation and discussion of proposed <i>C. elegans</i> health span assays and more disease-specific assays are presented to offer guidance for scientists intending to work with <i>C. elegans</i>, thus facilitating the initial steps towards the integration of <i>C. elegans</i> assays in their laboratories.

Roberts TM et al. (1997) Trends in Cell Biology "Nematode sperm: Ameboid movement without actin."

Stewart M, Roberts TM

[Trends in Cell Biology, 1997]

Nematodes produce amoeboid sperm that crawl over surfaces in a manner reminiscent of many actin-rich cells. However, These sperm contain no F-actin, and their motility is powered by a dynamic filament system composed of polymers of the 14-kDa major sperm protein (MSP). These simple cells use this unique motility apparatus exclusively for locomotion. Recent studies have capitalized on this feature to explore the key structural properties of MSP related to its role in motility and to reconstitute the motility apparatus both in vivo and in vitro. This review discusses how these investigations have laid the foundation for understanding the physical basis of amoeboid movement by identifying the mechanistic properties shared by the MSP-based machinery and the more familiar actin-based systems.

Blackwell TK et al. (2019) Genetics "TOR Signaling in Caenorhabditis elegans Development, Metabolism, and Aging."

Han M, Wu Z, Sewell AK, Blackwell TK

[Genetics, 2019]

The <b>T</b>arget <b>o</b>f <b>R</b>apamycin (TOR or mTOR) is a serine/threonine kinase that regulates growth, development, and behaviors by modulating protein synthesis, autophagy, and multiple other cellular processes in response to changes in nutrients and other cues. Over recent years, TOR has been studied intensively in mammalian cell culture and genetic systems because of its importance in growth, metabolism, cancer, and aging. Through its advantages for unbiased, and high-throughput, genetic and <i>in vivo</i> studies, <i>Caenorhabditis elegans</i> has made major contributions to our understanding of TOR biology. Genetic analyses in the worm have revealed unexpected aspects of TOR functions and regulation, and have the potential to further expand our understanding of how growth and metabolic regulation influence development. In the aging field, <i>C. elegans</i> has played a leading role in revealing the promise of TOR inhibition as a strategy for extending life span, and identifying mechanisms that function upstream and downstream of TOR to influence aging. Here, we review the state of the TOR field in <i>C. elegans</i>, and focus on what we have learned about its functions in development, metabolism, and aging. We discuss knowledge gaps, including the potential pitfalls in translating findings back and forth across organisms, but also describe how TOR is important for <i>C. elegans</i> biology, and how <i>C. elegans</i> work has developed paradigms of great importance for the broader TOR field.

Quinn CC et al. (2008) Trends Cell Biol "Axon guidance: asymmetric signaling orients polarized outgrowth."

Wadsworth WG, Quinn CC

[Trends Cell Biol, 2008]

A network of connections is established as neural circuits form between neurons. To make these connections, neurons initiate asymmetric axon outgrowth in response to extracellular guidance cues. Within the specialized growth cones of migrating axons, F-actin and microtubules asymmetrically accumulate where an axon projects forward. Although many guidance cues, receptors and intracellular signaling components that are required for axon guidance have been identified, the means by which the asymmetry is established and maintained is unclear. Here, we discuss recent studies in invertebrate and vertebrate organisms that define a signaling module comprising UNC-6 (the Caenorhabditis elegans ortholog of netrin), UNC-40 (the C. elegans ortholog of DCC), PI3K, Rac and MIG-10 (the C. elegans ortholog of lamellipodin) and we consider how this module could establish polarized outgrowth in response to guidance cues.

Lohmer LL et al. (2014) Cell Adh Migr "Invadopodia and basement membrane invasion in vivo."

Sherwood DR, Hagedorn EJ, Kelley LC, Lohmer LL

[Cell Adh Migr, 2014]

Over 20 years ago, protrusive, F-actin-based membrane structures, termed invadopodia, were identified in highly metastatic cancer cell lines. Invadopodia penetrate artificial or explanted extracellular matrices in 2D culture conditions and have been hypothesized to facilitate the migration of cancer cells through basement membrane, a thin, dense, barrier-like matrix surrounding most tissues. Despite intensive study, the identification of invadopodia in vivo has remained elusive and until now their possible roles during invasion or even existence have remained unclear. Studies in remarkably different cellular contexts-mouse tumor models, zebrafish intestinal epithelia, and C. elegans organogenesis-have recently identified invadopodia structures associated with basement membrane invasion. These studies are providing the first in vivo insight into the regulation, function, and role of these fascinating subcellular devices with critical importance to both development and human disease.