Advances in Cell biology, vol. 32, 2005, issue 1

Summary: Disorders in a unique type of posttranslational modification of a-dystroglycan lay at a background of a group of congenital muscular dystrophies, called dystroglycanopathies. To bind laminin in a basal membrane the protein has to be glycosylated in a special way, with mannose linked with O-glycosidic bond to serine or threonine in a mucin-like region. The nascent glycan is then elongated with N-acetylglucosamine, galactose, sialic acid and optionally fucose. It is also suggested that proper function of dystroglycan depends on mannose phosphorylation. Six genes are involved in the molecular pathogenesis of dystroglycanopathies: POMT-1, POMT-2, POMGnT-1, FKT, FKRP and LARGE. The former three are proved, and the further putative glycosyltransferases of O-mannosylation pathway. The mechanisms of dystroglycanopathy once again underline the peculiar regulatory role of glycosylation, indispensable for a proper function of particular proteins.

Key words: muscular dystrophy, dystroglycan, dystroglycanopathy, glycosylation, O-mannosylation, glycosyltransferases

Summary: In this paper the current opinions on the structure and function of the „lipid rafts” – heterogeneous, sterols and sphingolipids rich microdomains that occur in the plasma membrane but also in the membranes of some intracellular organelles e.g. Golgi complex, endoplasmic reticulum or mitochondria were presented. Lipid rafts have different dimensions. Their diameters often range from 50 to 100 nm, but larger forms with diameters of 200–500 nm also exist. The smallest lipid raft with diameter of 5 nm lipid raft contains approximately 30–40 lipids and 6–10 characteristic proteins. In spite of the small size of a single raft, the overall surface area of all lipid rafts accounts for approximately 30% of the entire surface of the plasma membrane. Depending of contents (mainly cholesterol) and protein-protein and protein-lipid interactions small rafts may coalesce to form structures 500 nm in diameter. Initially, lipid rafts were regarded as stable structures, that undergo only slow and slight temporal changes. As follows from the most recent experiments, these structures have been found to be highly dynamic, that constantly change their composition and play an important role in various biological processes. Moreover, it has been demonstrated that the same molecules occurring in the microdomains have different functions depending on which side of the plasma membrane (external or internal (cytoplasmic)) they appear. They may also translocate from one side to the other. The change of a position within the cytoplasmic and external sides of membrane depends on the amount of cholesterol and other lipids in the rafts, while the change of composition may take nanoseconds only. Lipid rafts were found to participate many cellular processes such as signal transduction, clathrin-independent (caveolar) endocytosis and others.

Key words: lipid rafts, microdomains, biological membranes

Summary: For a long time apoptosis has been considered the only type of programmed cell death responsible for the maintenance of homeostasis in the organism. However, the results of studies, which have been carried out for the last years, prove that depending on its type, the cell can be guided in different directions, which can result either in its survival or death. According to the NCCD Committee, apoptosis and autophagy are ranked as two types of cell death. The cell death, depending on its localization and its mechanism, has been divided into several subtypes and newly recognized types, such as: mitotic catastrophe, anoikosis, paraptosis, degeneration of Wallerian, entosis and cornification. This review was mainly focused on the characterization of mentioned processes with special attention paid to apoptosis, autophagy and detection methods. Moreover, a different view on the connections between programmed and unprogrammed cell death has been presented. The detection methods concerning different types of cell death in general can be divided into microscopic methods that allow the observation of typical morphological changes, and biochemical methods, based on the detection of extracellular and intracellular indicators. In spite of many available detection techniques, the distinction between particular types of cell death, both programmed and unprogrammed, often becomes impossible. For that reason, the NCCD Committee recommended to apply at least two detection methods (for example: microscopic and biochemical). Nevertheless, there are findings which suggest that many types of cell death should rather be considered as its stages and should not be divided into different processes.

Key words: programmed cell death, apoptosis, autophagy, detection methods

Summary: Endoparasitic sedentary nematodes infecting plant roots are an important problem of modern agriculture. In a compatible interaction with their hosts, cyst nematodes use stylet for mechanical root penetration. The specialized nematode oesophageal glands produce and secrete proteins that facilitate the migration within the root and change morphogenetic program of plant cells. The changes in selected initial cell involve cell cycle reactivation, cell wall modification and boosting of plant primary and secondary metabolism. These leads to the multinuclear syncytium formation, which is the nematode feeding site. Cyst nematode infection activate different plant defense responses, but their active suppression was also observed. The deep understanding of cellular mechanisms involved in syncytium development is essential for the development of new strategies for plant protection against these difficult to control pests.

Key words: cyst nematodes, syncytium, cell wall, cell cycle, auxin, plant defence

Summary: Immune cells infiltrate tumors and make up a significant component of the multicellular cancer microenvironment, yet the immune system often fails to prevent tumor formation and progression. One explanation for this paradox is the presence of tolerance-promoting regulatory T cells (Tregs). Tregs were known to be essential for maintaining self-tolerance. Tregs have been found to promote tolerance to tumors in mouse models. Treg infiltration in human tumors and malignant ascites is associated with worse clinical outcomes for various types of cancers. This review focuses on the cellular and molecular mechanisms by which Tregs influence antitumor immune responses, and also discusses how these mechanisms might be exploited to develop innovative immune-based approaches that can improve cancer therapy.

Summary: The discovery and use of antibiotics to fight against bacterial infection have let to overrun many diseases. However overuse and/or incorrect use of the antibiotics increase the concentration of these compounds in the environment and create the selective pressure, which promotes antibiotic resistant microorganisms. Multidrug resistant pathogenic bacteria are a huge problem of the modern medical science because of the infections, which they cause, are almost incurable. Researches show that the one of the most important mechanism responsible for the multidrug resistance in bacteria is the active transport (efflux system) of the antibiotics out of the cell. Bacterial drug efflux transporters are classified into the five groups: SMR (Small Multidrug Resistance), MFS (Major Facilitator Superfamily), RND (Resistance-Nodulation-Cell Division), MATE (Multidrug And Toxic Compound Extrusion) and ABC transporters (ATP-binding Cassette Superfamily). Currently scientists are working on recognition of molecular mechanisms of these transporters action, detection of their spatial structure and creation the model of drug transport. Additionally, new strategy of elimination of multidrug resistant bacteria focus on detecting of efflux pump inhibitors. It seems to be promising future strategy to control the bacterial diseases.

Key words: cantibiotic resistance, multidrug resistance, efflux system, SMR, MFS, RND, MATE, ABC transporters

Summary: For decades the way of viewing of the cell membrane has changed considerably. At the beginning of the twentieth century the cell membrane was visualized as a lipid bilayer. Following researches have discovered that the cell membrane contains also proteins. In 1972 Singer and Nicolson introduced the division of membrane proteins into peripheral and integral proteins. Singer and Nicolson had also conducted research on cells fusion, which have laid the foundation of the membrane model as a fluid mosaic of lipids and proteins. The Singer and Nicolson model in many aspects is still valid. Nowadays it is well known that membranes contain differently arranged regions which are called membrane domains. The study of the membrane domains is extremely fascinating but also a difficult challenge, because the results depend on methods used in the research. Based on numerous studies it can be concluded that the membrane domains are involved in the regulation of several biological processes such as cell adhesion, sorting and transport of lipids and proteins, and also signal transduction. The latter process is controlled by lipid rafts in which facilitated interaction between proteins and lipids have been observed. It should be remembered that ceramide-enriched microdomains and glycosynapses are included among membrane domains. The variety and diversity of membranes domains make membrane biology very complex but also very interesting an object of research.

Keywords: lipid rafts, membrane domains, detergent resistant membranes, model membranes

Hipocretins (Orexins) and their Receptors: Structure, Localization and Molecular Mechanisms of Actions

Summary: This paper illustrates elements of innate immunity, such as recently described natural T_H2 cells (nT_H2 or NHC), nuocytes, innate type 2 helper cells (Ih2), multi-potent progenitor type 2 cells (MMP^type2cells), and IL-36 that is very similar to IL-36. Populations of these cells are involved in the development of Th2 cytokine responses and participate in course of allergic processes and in host defense against microorganisms and parasites. All four populations lack expression of surface markers characteristic for T cells, B cells, NK cells, neutrophils, macrophages and dendritic cells. These cells differ in their anatomical localization, phenotype and their function. In turn IL-36 and IL-37 are the inhibitors of innate immunity primarily through suppression of production of proinflammatory cytokines.

Key words: innate immunity, nT_H2 cells, nuocytes, Ih2 cells, MMPtype2 cells, IL-36, IL-37