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

Summary: Myogenic cells are potential muscle cells which divide mitotically. Following their exit from the cell cycle at phase G1/G0 they enter the stage of post-mitotic myoblasts. Expression of regulatory proteins of MRF family (MyoD, Myf5, myogenin and MRF-4), which form heterodimers with E family proteins E (E12 and E47) aided by MEF family proteins, starts in their nuclei. The system activates muscle-specific genes. Before the fusion the myoblasts elongate, become linearly arranged, adhere to each other and fuse into an elongated myotube. Transmembrane proteins, e.g. cadherins and integrins, participate in adhesion and fusion. Myogenic cells of non-segmented mesoderm and of newly formed somites are affected by signal proteins, Shh and Wnt, emitted from the neighbouring tissues. These proteins trigger the activity of genes of MRF family, Myf5 and MyoD. Besides, myogenic cells display a great morphogenetic mobility. In Amniota they translocate under the dermatomyotome. Pioneer myoblasts of the myotome grow and elongate. In some amphibian species during somitogenesis myogenic cells rotate from the perpendicular position to the position parallel to the body axis. In other amphibians they elongate along the body axis. As a result of rotation and elongation they occupy the whole length of the myotome and then differentiate into mononucleate myotubes. In fishes myogenic cells of non-segmented mesoderm migrate from paraxial position onto the myotome surface, while „external cells” migrate into the myotome. In amphibians and fishes mesenchymal cells migrate into the myotomes via miosepts. Myoblasts of mesenchymal origin fuse with the myotube. Moreover, myogenic cells are capable of migration for rather long distances. In Amniota cells of the ventral lip of dermatomyotome, and in lower chordates cells of the ventral part of the somite migrate e.g. to primordial limbs, fins and ventral muscles. The migrating cells show an expression of regulatory proteins Pax3 and Lbx1.

Summary: Coffin-Lowry syndrome (CLS, MIM#303600) is an X-linked semidominant disorder. In males disorder is characterized by severe mental retardation with distinctive phenotype of face and hands, and with abnormalities in osteoarticular system. In females the intensity of symptoms is variable. Coffin-Lowry syndrome is caused in the majority of cases by mutations in the RSK2 gene (RPS6KA3) located in Xp22.2 region. The RSK2 gene encodes for RSK2 protein that belongs to a family of serine-threonine kinases acting in the MAPK/ERK signalling pathway. RSK2 protein consists of 740 amino acids and is composed of two kinase domains. RSK proteins are involved in various processes responsible for cellular proliferation and differentiation, cellular stress response, and apoptosis. Up to now about 130 different mutations in the RSK2 gene in 160 patients with Coffin-Lowry syndrome have been identified. Two-thirds of the identified mutations cause the premature introduction of a termination codon, leading to the absence of the functional serine-threonine kinase. Eighty percent of all identified mutations appeared de novo. The detectability of mutations in the RSK2 gene is about 40%. Mental retardation characteristic for Coffin-Lowry syndrome is caused by the absence of the functional RSK2 protein in the MAPK/ERK signalling pathway, involved in creating new synaptic junctions and long-term memory modeling. Abnormalities in the phosphorylation of the transcription factor ATF4 are responsible for creating defects in skeletal system.

Key words: Coffin-Lowry syndrome (CLS), RSK2 gene, RSK2 protein, mutations, MAPK/ERK signal

Summary: The presented paper reviews the latest literature data on SMCs proteins (Structural Maintenance of Chromosomes) which contribute to regular chromatid segregation in mitosis and meiosis. SMC proteins are high molecular weight proteins with ATPase activity. These proteins are highly conserved in eukaryotes and prokaryotes. The structure of SMCs proteins is very specific, each SMC subunit contais two globular domains and a helical domain, called arm. Conservative motifs Walker A and Walker B are located at the N-terminal and C-terminal ends of the head domain. ATP binds to Walker A and Walker B of one subunit and the C-motif of the second subunit. C-motif is a part of C-terminal domain. SMCs can be classified into subfamilies, which associate with one another in particular pairs to perform their specific functions. SMCs are crucial components of condensins and cohesins. A single condensin or cohesin particle is composed of SMCs heterodimer and 3 or 2 non-SMC proteins, respectively. Cohesins are four-subunit complexes MCD1/RAD21/SCC1, SMC1, SMC3 i SCC3/SA1/SA2. The role of cohesins is holding sister chromatids together during mitosis and meiosis. They consists of SMC1-SMC3 heterodimer and Scc1 subunit which connects the head domains of SMC1 and SMC3, altogether forming a tripartite ring-like structure. Two models for the action of cohesin were proposed. One of them is referred as an embrace model. According to this cohesin complexes embrace two DNA duplexes to hold the sister chromatids together until metaphase. Proteolytic cleavage of Scc1 by separase at the start of anaphase opens the ring and release two sister chromatids. Condensins play key role in chromosomes condensation. They are five-subunit complexes containing SMC2-SMC4 heterodimer. This constitues the core of two types of condensin complexes, condensin I and condensin II. The condensin II associates with chromatin in prophase. Condensin I is cytoplasmic and interact with chromosomes after nuclear envelope breakdown. Condensin II is required for chromosome condensation in early prophase, whereas condensin I is required for the complete dissociation of cohesin from chromosome arms, for chromosome compaction and for normal timing of progression through metaphase. Therefore both types are essential for proper chromosome segregation. Except for condensines and cohesines, there are other proteins which are important in chromosome segregation. Another protein required for proper chromosome segregation is SUMO. The SUMO is small ubiquitin related modifier is a member ubiquitin-like protein family. SUMO is engaged in cyclosome regulation. Cyclosome (APC/C – Anaphase Promoting Complex /Cyclosom), causes degradation of securine, which release separase and affect the conformation of Pds5 protein setting free cohesins. CENP-F is a facultative centromeric protein, which in cooperation with other centromeric proteins and mitotic spindle checkpoint proteins affects chromosome segregation.

Key words: SMC, cohesin, condensin, SUMO, CENP-F

Summary: Alzheimer's disease is one of the most widespread neurodegenerative disorder. The etiology of this disease is not completely elucidated. Amyloid plaques (extracellular aggregates of amyloid b peptides – Ab) and neurofibrillary tangles (intracellular deposits of hyperphosphorylated tau protein) are histopathological hallmarks of the Alzheimer disease. These morphological changes are present mostly in brain regions involved in cognition, emotion, learning and memory. The critical events in the pathogenesis of Alzheimer's disease are caused by amyloid b peptides. The mechanism of the neurotoxicity of Ab has not yet been fully defined. Ab peptides have been reported to mediate dysfunction of mitochondria, production of reactive oxidative species and disruption of cell membrane permeability. Proteolytic processing of the amyloid precursor protein (APP) by b- and c-secretase is the initial step in the production of the amyloid b peptide, it occurs throughout the whole life. Attenuated mechanisms of the Ab maintenance on non-toxic level in the brain, is the main cause of Alzheimer's disease. The genetics and environmental risk factors associated with this disorder have been characterized. Moreover, Ab permanently presented in brain of people suffering from Alzheimer's disease stimulates chronic inflammatory reaction, which might contribute to death of neurons. However, many evidences indicate that mediators of inflammatory reaction have beneficial effects on neuron survival in Alzheimer's disease. The contribution of inflammatory processes to Alzheimer's disease remains to be elucidated. Recently, the rapid progress towards understanding of Alzheimer's disease molecular mechanisms have been made. On the basis of current knowledge many new therapeutics strategies are developed.

Key words: Alzheimer's Disease, neurodegeneration, amyloid b peptides, Tau protein, inflammation, cytokines

Summary: Activation of innate, antigen-unspecific effector immunological mechanisms in mammals proceeds on different levels of molecular phenomena in an infected cell. One of such an important, although only partly recognized processes which take part in the elimination of infections caused by viruses and intracellular bacteria is autophagy. The process is activated through the above mentioned infectious agents, autophagic vacuoles sequester bacteria, and viruses delivering them to lysosomal degradation. Yet pathogens developed the ability of an efficient „immunological escape” from autophagy which enables them to omit effector mechanisms of an infected organism.

Summary: The unique feature of plant organisms is the presence of plasmodesmata (PD) between neighboring cells. Such plasmodesmatal continuum which exists within the plant body is termed symplasm. Classical view of plasmodesmata as static structures within the cell walls between neighboring cells must be reevaluated. According to our recent knowledge symplast is divided into functional domain. It appeared that symplasmic isolation/communication of cells or group of cells (symplasmic domains or symplasmic fields) is necessary for its proper differentiation within the plant body. Namely, plasmodesmata as a highly flexible structures regulate the diffusion of molecules including proteins and mRNA. This confirms the role of PD in the regulation of cells differentiation. For better understanding the role of symplasmic isolation/communication in cell differentiation basic information about plasmodesmata, symplasm and symplasmic transport are also described in presented paper. Some parameters of molecules diffusion in water, through plasmalemma and plasmodesmata, dynamic of plasmodesmata closure and opening (synthesis of callose and its digestion) under different conditions were also provided. Information about movement of proteins (KNOTTED 1, DEFICIENS, CLAVATA 3, LEAFY, APETALA 3) and RNA between different zones of apical meristem (tunica and corpus) were described in details, as these results were among the first which suggested that movement of signaling molecules through plasmodesmata exist and can influence cell differentiation. In presented article information about the role of symplasmic isolation during the differentiation of trichoblast and atrichoblast cells, changes within the embryo sac in connection with the fertilization, double fertilization, zygote and seed development were described. During the differentiation of trichoblasts and atrichoblasts the importance of signals movement between cells through plasmodesmata and changes in symplasmic communication were described on the example of Arabidopsis root [13, 78]. Genetic control of hair cells differentiation and the role of symplasmic communication in this process were also shown. In the case of embryo sac development of Torenia fournieri results from experiments where symplasmic communication was investigated with the use of fluorochrome of low molecular weight (LYCH) and dextrans (3, 10 and 40 kDa) were described [12, 22]. During the development of Arabidopsis thaliana seed, changes in plasmodesmata SEL were also shown [77]. The importance of symplasmic communication during zygotic and somatic embryogenesis were briefly described on the example of Arabidopsis embryo development. Presented article shows information about the symplasmic isolation between explantat and somatic embryo. Moreover, description of the analysis of ise2 mutants in connection with the symplasmic isolation was also presented. From all described examples it is evident that cell differentiation is connected with the decrease of the symplasmic communication between cells which undergo different fate during the development. It is also important to notice that plasmodesmata are not passive channels, but critical players in gene regulation, controlling intercellular transport of molecules between particular cells during development [94].

Key words: cell differentiation, symplasmic domains, symplasmic isolation, symplasmic transport

Summary: A bulk of biochemical pathways, which play a crucial role in such processes as protection of cells from oxidative stress, cellular proliferation or selenium metabolism are regulated by thioredoxin - thioredoxin reductase system. This system consists of two groups of enzymatic proteins which require NADPH for their activity. NADPH is acquired mainly from pentose phosphate pathway. Proteins from thioredoxin family can be found in all organisms. Moreover, a number of viral products exploit thioredoxin - thioredoxin reductase system for their replication. It has been shown, that various splicing forms of thioredoxin may exert unique physiological functions, for instance in the regulation of the immune response. Recently, a growing number of reports revealed that this system participates in several stages of carcinogenesis and can affect the outcome of standard antitumor treatments.