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.

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.

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.

Caffrey CR et al. (2018) PLoS Negl Trop Dis "Cysteine proteases as digestive enzymes in parasitic helminths."

Caffrey CR, Smith D, Dalton JP, Rebello KM, Goupil L

[PLoS Negl Trop Dis, 2018]

We briefly review cysteine proteases (orthologs of mammalian cathepsins B, L, F, and C) that are expressed in flatworm and nematode parasites. Emphasis is placed on enzyme activities that have been functionally characterized, are associated with the parasite gut, and putatively contribute to degrading host proteins to absorbable nutrients [1-4]. Often, gut proteases are expressed as multigene families, as is the case with Fasciola [5] and Haemonchus [6], presumably expanding the range of substrates that can be degraded, not least during parasite migration through host tissues [5]. The application of the free-living planarian and Caenorhabditis elegans as investigative models for parasite cysteine proteases is discussed. Finally, because of their central nutritive contribution, targeting the component gut proteases with small-molecule chemical inhibitors and understanding their utility as vaccine candidates are active areas of research [7].

Xavier CP et al. (2008) Subcell Biochem "Evolutionary and functional diversity of coronin proteins."

Clemen CS, Xavier CP, Fernandez MP, Morgan RO, Eichinger L

[Subcell Biochem, 2008]

This chapter discusses various aspects of coronin phylogeny, structure and function that are of specific interest. Two subfamilies of ancient coronins of unicellular pathogens such as Entamoeba, Trypanosoma, Leishmania and Acanthamoeba as well as of Plasmodium, Babesia, and Trichomonas are presented in the first two sections. Their coronins generally bind to F-actin and apparently are involved in proliferation, locomotion and phagocytosis. However, there are so far no studies addressing a putative role of coronin in the virulence of these pathogens. The following section delineates genetic anomalies like the chimeric coronin-fusion products with pelckstrin homology and gelsolin domains that are found in amoeba. Moreover, most nonvertebrate metazoa appear to encode CRN8, CRN9 and CRN7 representatives (for these coronin symbols see Chapter 2), but in e.g., Drosophila melanogaster and Caenorhabditis elegans a CRN9 is missing. The forth section deals with the evolutionary expansion of vertebrate coronins. Experimental data on the F-actin binding CRN2 of Xenopus (Xcoronin) including a Cdc42/Rac interactive binding (CRIB) motif that is also present in other members of the coronin protein family are discussed. Xenopus laevis represents a case for the expansion of the seven vertebrate coronins due to tetraploidization events. Other examples for a change in the number of coronin paralogs are zebrafish and birds, but (coronin) gene duplication events also occurred in unicellular protozoa. The fifth section of this chapter briefly summarizes three different cellular processes in which CRN4/CORO1A is involved, namely actin-binding, superoxide generation and Ca(2+)-signaling and refers to the largely unexplored mammalian coronins CRN5/CORO2A and CRN6/CORO2B, the latter binding to vinculin. The final section discusses how, by unveiling the aspects of coronin function in organisms reported so far, one can trace a remarkable evolution and diversity in their individual roles anticipating a rather complex and intricate involvement of coronins in a variety of cellular processes.

Aguilar PS et al. (2013) Trends Genet "Genetic basis of cell-cell fusion mechanisms."

Podbilewicz B, Helming L, Fleissner A, Aguilar PS, Inoue N, Wang H, Baylies MK, Wong M

[Trends Genet, 2013]

Cell-cell fusion in sexually reproducing organisms is a mechanism to merge gamete genomes and, in multicellular organisms, it is a strategy to sculpt organs, such as muscle, bone, and placenta. Moreover, this mechanism has been implicated in pathological conditions, such as infection and cancer. Studies of genetic model organisms have uncovered a unifying principle: cell fusion is a genetically programmed process. This process can be divided in three stages: competence (cell induction and differentiation); commitment (cell determination, migration, and adhesion); and cell fusion (membrane merging and cytoplasmic mixing). Recent work has led to the discovery of fusogens, which are cell fusion proteins that are necessary and sufficient to fuse cell membranes. Two unrelated families of fusogens have been discovered, one in mouse placenta and one in Caenorhabditis elegans (syncytins and F proteins, respectively). Current research aims to identify new fusogens and determine the mechanisms by which they merge membranes.

Yang Y et al. (2015) Korean J Parasitol "Serine proteases of parasitic helminths."

Vallee I, Cheng SP, Liu MY, Yang Y, Boireau P, Cai YN, Wen YJ

[Korean J Parasitol, 2015]

Serine proteases form one of the most important families of enzymes and perform significant functions in a broad range of biological processes, such as intra- and extracellular protein metabolism, digestion, blood coagulation, regulation of development, and fertilization. A number of serine proteases have been identified in parasitic helminths that have putative roles in parasite development and nutrition, host tissues and cell invasion, anticoagulation, and immune evasion. In this review, we described the serine proteases that have been identified in parasitic helminths, including nematodes (Trichinella spiralis, T. pseudospiralis, Trichuris muris, Anisakis simplex, Ascaris suum, Onchocerca volvulus, O. lienalis, Brugia malayi, Ancylostoma caninum, and Steinernema carpocapsae), cestodes (Spirometra mansoni, Echinococcus granulosus, and Schistocephalus solidus), and trematodes (Fasciola hepatica, F. gigantica, and Schistosoma mansoni). Moreover, the possible biological functions of these serine proteases in the endogenous biological phenomena of these parasites and in the host-parasite interaction were also discussed.