Primakoff P et al. (2000) Trends Genet "The ADAM gene family: surface proteins with adhesion and protease activity."

Primakoff P, Myles DG

[Trends Genet, 2000]

An ADAM is a transmembrane protein that contains a disintegrin and metalloprotease domain and, therefore, it potentially has both cell adhesion and protease activities. Currently, the ADAM gene family has 29 members, although the function of most ADAM gene products is unknown. We discuss the ADAM gene products with known functions that act in a highly diverse set of biological processes, including fertilization, neurogenesis, myogenesis, embryonic TGF-alpha release and the inflammatory response.

Kubota Y et al. (2006) Biol Chem "C. elegans as a model system to study the function of the COG complex in animal development."

Nishiwaki K, Kubota Y

[Biol Chem, 2006]

The conserved oligomeric Golgi (COG) complex is an octameric protein complex associated with the Golgi apparatus and is required for proper sorting and glycosylation of Golgi resident enzymes and secreted proteins. Although COG complex function has been extensively studied at the cellular and subcellular levels, its role in animal development mostly remains unknown. Recently, mutations in the components of the COG complex were found to cause abnormal gonad morphogenesis in Caenorhabditis elegans. In C. elegans, the COG complex acts in the glycosylation of an ADAM (a disintegrin and metalloprotease) family protein, MIG-17, which directs migration of gonadal distal tip cells to lead gonad morphogenesis. This is the first link between the COG complex and the function of an ADAM protease that is directly involved in organ morphogenesis, demonstrating the potential of C. elegans as a model system to study COG function in animal development.

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

Best AM et al. (2018) Cell Microbiol "Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts by Legionella pneumophilla."

Best AM, Kwaik YA

[Cell Microbiol, 2018]

Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped more sophisticated innate defense mechanisms than protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defense processes. Not surprisingly, the majority of proteins involved in phagosome biogenesis (~80%) have origins in the phagotrophy stage of evolution. There are a plethora of highly evolved cellular and innate metazoan processes, not represented in Protist biology, that are modulated by L. pneumophila; including TLR2 signaling, NF-B, apoptotic and inflammatory processes, histone modification, caspases, and the NLRC-Naip5 inflammasomes. Importantly, L. pneumophila infects hemocytes of the invertebrate Galleria mellonella, kill G. mellonella larvae, and proliferate in and kill Drosophila adult flies and Caenorhabditis elegans. Although co-evolution with protist hosts has provided a substantial blueprint for L. pneumophila to infect macrophages, we discuss the further evolutionary aspects of co-evolution of L. pneumophila and its adaptation to modulate various highly evolved innate metazoan processes prior to becoming a human pathogen.

Lee SK et al. (2013) Int J Biochem Cell Biol "Dicarbonyl/l-xylulose reductase (DCXR): The multifunctional pentosuria enzyme."

Ahnn J, Lee SK, Son LT, Choi HJ

[Int J Biochem Cell Biol, 2013]

Dicarbonyl/L-xylulose reductase (DCXR) is a highly conserved and phylogenetically widespread enzyme converting L-xylulose into xylitol. It also reduces highly reactive -dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. Enzymatic properties of DCXR from yeast, fungi and mammalian tissue extracts are extensively studied. Deficiency of the DCXR gene causes a human clinical condition called pentosuria and low DCXR activity is implicated in age-related diseases including cancers, diabetes, and human male infertility. While mice provide a model to study clinical condition of these diseases, it is necessary to adopt a physiologically tractable model in which genetic manipulations can be readily achieved to allow the fast genetic analysis of an enzyme with multiple biological roles. Caenorhabditis elegans has been successfully utilized as a model to study DCXR. Here, we discuss the biochemical properties and significance of DCXR activity in various human diseases, and the utility of C. elegans as a research platform to investigate the molecular and cellular mechanism of the DCXR biology.

Cuasnicu PS et al. (2001) Arch Med Res "Molecular mechanisms involved in mammalian gamete fusion."

Da Ros VG, Cohen DJ, Morgenfeld MM, Busso D, Cuasnicu PS, Ellerman DA

[Arch Med Res, 2001]

Fusion between gametes is a key event in the fertilization process involving the interaction of specific domains of the sperm and egg plasma membranes. During recent years, efforts have been made toward the identification of the specific molecular components involved in this event. The present work will focus on the best characterized candidates for mediating gamete membrane fusion in mammals. These molecules include members of the ADAM (a disintegrin and a metalloprotease domain) family, i.e., testicular proteins fertilin alpha, fertilin beta, and cyritestin, which are thought to interact with integrins in the egg plasma membrane through their disintegrin domains, and a member of the cysteine-rich secretory proteins (CRISP) family, i.e., epididymal protein DE, which participates in an event subsequent to sperm-egg binding and leading to fusion through specific complementary sites localized on the fusogenic area of the egg surface. The identification and characterization of these molecules will contribute not only to a better understanding of the molecular mechanisms underlying mammalian sperm-egg fusion but also to the development of new methods for both fertility regulation and diagnosis and treatment of human infertility.

Lv Z et al. (2015) Parasitol Res "Genome mining offers a new starting point for parasitology research."

Wu Z, Ji P, Li H, Cai Y, Zhang L, Luo S, Wang H, Lv Z

[Parasitol Res, 2015]

Parasites including helminthes, protozoa, and medical arthropod vectors are a major cause of global infectious diseases, affecting one-sixth of the world's population, which are responsible for enormous levels of morbidity and mortality important and remain impediments to economic development especially in tropical countries. Prevalent drug resistance, lack of highly effective and practical vaccines, as well as specific and sensitive diagnostic markers are proving to be challenging problems in parasitic disease control in most parts of the world. The impressive progress recently made in genome-wide analysis of parasites of medical importance, including trematodes of Clonorchis sinensis, Opisthorchis viverrini, Schistosoma haematobium, S. japonicum, and S. mansoni; nematodes of Brugia malayi, Loa loa, Necator americanus, Trichinella spiralis, and Trichuris suis; cestodes of Echinococcus granulosus, E. multilocularis, and Taenia solium; protozoa of Babesia bovis, B. microti, Cryptosporidium hominis, Eimeria falciformis, E. histolytica, Giardia intestinalis, Leishmania braziliensis, L. donovani, L. major, Plasmodium falciparum, P. vivax, Trichomonas vaginalis, Trypanosoma brucei and T. cruzi; and medical arthropod vectors of Aedes aegypti, Anopheles darlingi, A. sinensis, and Culex quinquefasciatus, have been systematically covered in this review for a comprehensive understanding of the genetic information contained in nuclear, mitochondrial, kinetoplast, plastid, or endosymbiotic bacterial genomes of parasites, further valuable insight into parasite-host interactions and development of promising novel drug and vaccine candidates and preferable diagnostic tools, thereby underpinning the prevention and control of parasitic diseases.

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].

Wojtkowiak A (2007) Wiad Parazytol "[The investigations of the role of toll-like receptors (TLR) in host response to parasitic infection on the current background regarding TLR in mammals and the model nematode Caenorhabditis elegans]"

Wojtkowiak A

[Wiad Parazytol, 2007]

Toll-like receptors (TLRs) are amongst the most highly conserved in the evolution of receptor family, being found in both immune and other cells. TLRs were observed in vascular endothelial cells, epithelial cells, microglia cells, adipocytes, and intestinal and renal cells. TLRs plays a key role in the innate immune response to a variety of pathogens. At present, very little is known about the role of TLRs in host defense against parasitic pathogen infections. The first study shows that TLRs contribute to both innate and adaptive immune responses following infection with protozoan parasite Leishmania major. The TLRs recognizing PAMPs associated with the parasite L. major are essential for the activation of the innate and adaptive immune responses to infection. A study concerning recognition of the role of TLRs in the host-parasite relationship would be an interesting challenge for future study.

Barnes TM (1994) Trends in Genetics "OPUS-A growing family of gap junction proteins?"

Barnes TM

[Trends in Genetics, 1994]

Recently, Krishnan et al. Reported the cloning and sequencing of the Drosophila shaking-B (shakB; alias Passover, or Pas) gene, required for the jump response to an optical stimulus. The predicted gene product was similar to those of both the Drosophila gene lethal (1) optic ganglion reduced [l(1)ogre] and the Caenorhabditis elegans gene unc-7, which together define a new family of evolutionarily conserved proteins that may be membrane-associated. Below I describe three additional members of this family, as identified by sequence homologies. An alignment of all these sequences permits a more informed prediction of the general structure of members of this family. The structure is that of a new type of multipass transmembrane protein. On the basis of the phenotypes of mutant organisms, I suggest that the encoded proteins may be members of a family of invertebrate