Volume 4 (2014): Issue 1 (March 2014)

Mechanisms of innate immunity are triggered as a result of recognition of evolutionarily conserved structures of microorganisms, named pathogen-associated molecular patterns. Their recognition is mediated by specialized receptors which initiate signalling cascades leading to expression of pro-inflammatory mediators and regulation of acquired immunity. Among several classes of such receptors, Toll-like receptors (TLRs) are extensively studied as they can sense an array of microbial cell wall and membrane components as well as single- and double-stranded RNA and DNA motifs typical for microorganisms. Each TLR consists of a ligand-binding domain containing leucine-rich repeats, a single transmembrane domain and a signalling TIR domain. After ligand binding, TLRs dimerize which facilitates the interaction of their TIR domains with adaptor proteins triggering signalling cascades. TLRs engage four common adaptor proteins, about ten signalling kinases, and a few transcription factors including NFκB, IRF and AP-1. In this review, special attention is paid to TLR4 activated by lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, since an exaggerated response to LPS may lead to potentially deadly septic shock. In recent years considerable progress has been made in the understanding of how the cooperation of several proteins, including CD14, TLR4/MD-2 complex and scavenger receptors, modulates the cell response to LPS. These studies have also revealed a dichotomy of signalling pathways triggered by TLR4 which depends on the participation of MyD88 and TRIF adaptor proteins and leads to the expression of genes encoding pro-inflammatory cytokines and type I interferons, respectively. The key event in the TRIF-dependent pathway is the internalization of activated TLR4.

The human insulin-like growth factor (IGF) system has attracted significant researcher interest due to its endocrine and autocrine / paracrine activities, mitogenic effects and the involvement in the regulation of proliferation, differentiation and apoptosis. The signaling pathways used by the IGF system impact cellular metabolism in a complex manner complex and many details are still unclear. Understanding the molecular mechanism of action of IGF’s and their effects on cellular activity may provide a basis to develop new anticancer drugs. This review focuses on recent studies that expand our knowledge of the signaling pathways of IGF system

UDP-glycosyltransferases (GTases, UGT) catalyze the transfer of the sugar moiety from the uridine-diphosphate-activated monosaccharide (e.g. uridine-diphosphate-5’-glucose, UDPG) molecule to the specific acceptor. Glycosides contain aglycons attached by a β-glycosidic bond to C1 of the saccharide moiety. Glycosylation is one of the mechanisms maintaining cellular homeostasis through the regulation of the level, biological activity, and subcellular distribution of the glycosylated compounds. The glycosides play various functions in plant cells, such as high-energy donors, or signalling molecules, and are involved in biosynthesis of cell walls. Plant cells exhibit structural and functional diversity of UGT proteins. The Arabidopsis thaliana genome contains more than 100 genes encoding GTases, which belong to 91 families, and are deposited in the CAZY (Carbohydrate Active enzyme) database (www. cazy.org/GlycosylTransferases.html). The largest UGT1 class is divided into 14 subfamilies (A-N), and includes proteins containing highly conserved 44-amino acid PSPG (Plant Secondary Product Glycosyltransferase) motif at the C-terminus. The PSPG motif is involved in the binding of UDP-sugar donors to the enzyme. UGT1’s catalyze the biosynthesis of both ester-type and ether-type conjugates of plant hormones (phytohormones). Conjugation of the phytohormones is an important mechanism that regulates the concentration of physiological active hormone levels during growth and development of plants. Glycoconjugation of phytohormones is widespread in the plant kingdom and all known phytohormones are able to form these conjugates. Most plant hormone conjugates do not indicate physiological activity, but rather are involved in transport, storage and degradation of the phytohormones. UDPG-dependent glycosyltransferases possess high substrate specificity, even within a given class of phytohormones. In many cases, the phenotype of plants is strongly affected by loss-of-function mutations in UGT genes. In this paper, advances in the isolation and characterization of glycosyltransferases of all plant hormones: auxin, brassinosteroids, cytokinin, gibberellin, abscisic acid, jasmonates, and salicylate is described

A few years ago, a so far unknown type of intercellular connections, involved in communication was discovered. Due to their specific nano-architecture, these connections were named membrane nanotubes or tunneling nanotubes. Nanotubes ensure the transfer of both membrane and cytosolic cellular components, including organelles. Nanotubes also participate in calcium signal transduction and apoptosis signal. The length of the distance at which cells contact via nanotubes reaches several hundred micrometers. The published data suggest that nanotubes have heterogeneous structure. Among them, there are nanotubes which provide direct contact of the cytoplasm in connected cells (open-ended structure), and those, in which the transport requires overcoming a barrier, which is the cell membrane (close-ended structure). An important finding in the study of membrane nanotubes was demonstrating the ability of these connections of the intercellular transfer of pathogens, such as HIV, or abnormal form of PrP prion protein. In addition, nanotubes mediate a transport of MDR protein, involved in resistance of cancer cells to chemotherapy. It means that this type of cell connection may play an important role in the pathomechanism of AIDS, prion as well as cancer diseases.