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Tight Regulation (tight + regulation)
Selected AbstractsRegulation of ligands for the activating receptor NKG2DIMMUNOLOGY, Issue 4 2007Anita R. Mistry Summary The outcome of an encounter between a cytotoxic cell and a potential target cell depends on the balance of signals from inhibitory and activating receptors. Natural Killer group 2D (NKG2D) has recently emerged as a major activating receptor on T lymphocytes and natural killer cells. In both humans and mice, multiple different genes encode ligands for NKG2D, and these ligands are non-classical major histocompatibility complex class I molecules. The NKG2D,ligand interaction triggers an activating signal in the cell expressing NKG2D and this promotes cytotoxic lysis of the cell expressing the ligand. Most normal tissues do not express ligands for NKG2D, but ligand expression has been documented in tumour and virus-infected cells, leading to lysis of these cells. Tight regulation of ligand expression is important. If there is inappropriate expression in normal tissues, this will favour autoimmune processes, whilst failure to up-regulate the ligands in pathological conditions would favour cancer development or dissemination of intracellular infection. [source] Consistent dynamics suggests tight regulation of biophysical parameters in a small network of bursting neuronsDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2006Attila Szücs Abstract The neuronal firing patterns in the pyloric network of crustaceans are remarkably consistent among animals. Although this characteristic of the pyloric network is well-known, the biophysical mechanisms underlying the regulation of the systems output are receiving renewed attention. Computer simulations of the pyloric network recently demonstrated that consistent motor output can be achieved from neurons with disparate biophysical parameters among animals. Here we address this hypothesis by pharmacologically manipulating the pyloric network and analyzing the emerging voltage oscillations and firing patterns. Our results show that the pyloric network of the lobster stomatogastric ganglion maintains consistent and regular firing patterns even when entire populations of specific voltage-gated channels and synaptic receptors are blocked. The variations of temporal parameters used to characterize the burst patterns of the neurons as well as their intraburst spike dynamics do not display statistically significant increase after blocking the transient K-currents (with 4-aminopyridine), the glutamatergic inhibitory synapses (with picrotoxin), or the cholinergic synapses (with atropine) in pyloric networks from different animals. These data suggest that in this very compact circuit, the biophysical parameters are cell-specific and tightly regulated. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Dynamics of cell wall structure in Saccharomyces cerevisiaeFEMS MICROBIOLOGY REVIEWS, Issue 3 2002Frans M Klis Abstract The cell wall of Saccharomyces cerevisiae is an elastic structure that provides osmotic and physical protection and determines the shape of the cell. The inner layer of the wall is largely responsible for the mechanical strength of the wall and also provides the attachment sites for the proteins that form the outer layer of the wall. Here we find among others the sexual agglutinins and the flocculins. The outer protein layer also limits the permeability of the cell wall, thus shielding the plasma membrane from attack by foreign enzymes and membrane-perturbing compounds. The main features of the molecular organization of the yeast cell wall are now known. Importantly, the molecular composition and organization of the cell wall may vary considerably. For example, the incorporation of many cell wall proteins is temporally and spatially controlled and depends strongly on environmental conditions. Similarly, the formation of specific cell wall protein,polysaccharide complexes is strongly affected by external conditions. This points to a tight regulation of cell wall construction. Indeed, all five mitogen-activated protein kinase pathways in bakers' yeast affect the cell wall, and additional cell wall-related signaling routes have been identified. Finally, some potential targets for new antifungal compounds related to cell wall construction are discussed. [source] Regulation of chondrocyte differentiation by the actin cytoskeleton and adhesive interactionsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2007Anita Woods Chondrocyte differentiation is a multi-step process characterized by successive changes in cell morphology and gene expression. In addition to tight regulation by numerous soluble factors, these processes are controlled by adhesive events. During the early phase of the chondrocyte life cycle, cell,cell adhesion through molecules such as N-cadherin and neural cell adhesion molecule (N-CAM) is required for differentiation of mesenchymal precursor cells to chondrocytes. At later stages, for example in growth plate chondrocytes, adhesion signaling from extracellular matrix (ECM) proteins through integrins and other ECM receptors such as the discoidin domain receptor (DDR) 2 (a collagen receptor) and Annexin V is necessary for normal chondrocyte proliferation and hypertrophy. Cell,matrix interactions are also important for chondrogenesis, for example through the activity of CD44, a receptor for Hyaluronan and collagens. The roles of several signaling molecules involved in adhesive signaling, such as integrin-linked kinase (ILK) and Rho GTPases, during chondrocyte differentiation are beginning to be understood, and the actin cytoskeleton has been identified as a common target of these adhesive pathways. Complete elucidation of the pathways connecting adhesion receptors to downstream effectors and the mechanisms integrating adhesion signaling with growth factor- and hormone-induced pathways is required for a better understanding of physiological and pathological skeletal development. J. Cell. Physiol. 213: 1,8, 2007. © 2007 Wiley-Liss, Inc. [source] Prostate carcinoma cells selected by long-term exposure to reduced oxygen tension show remarkable biochemical plasticity via modulation of superoxide, HIF-1, levels, and energy metabolismJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Jeanne Bourdeau-Heller Cancer cells are able to tolerate levels of O2 that are damaging or lethal to normal cells; we hypothesize that this tolerance is the result of biochemical plasticity which maintains cellular homeostasis of both energy levels and oxidation state. In order to examine this hypothesis, we used different O2 levels as a selective agent during long-term culture of DU145 prostate cancer cells to develop three isogenic cell lines that grow in normoxic (4%), hyperoxic (21%), or hypoxic (1%) O2 conditions. Growth characteristics and O2 consumption differed significantly between these cell lines without changes in ATP levels or altered sensitivity to 2-deoxy- D -glucose, an inhibitor of glycolysis. O2 consumption was significantly higher in the hyperoxic line as was the level of endogenous superoxide. The hypoxic cell line regulated the chemical gradient of the proton motive force (PMF) independent of the electrical component without O2 -dependent changes in Hif-1, levels. In contrast, the normoxic line regulated Hif-1, without tight regulation of the chemical component of the PMF noted in the hypoxic cell line. From these studies, we conclude that selection of prostate cancer cells by long-term exposure to low ambient levels of O2 resulted in cells with unique biochemical properties in which energy metabolism, reactive oxygen species (ROS), and HIF-1, levels are modulated to allow cell survival and growth. Thus, cancer cells exhibit remarkable biochemical plasticity in response to various O2 levels. J. Cell. Physiol. 212:744,752, 2007. © 2007 Wiley-Liss, Inc. [source] Function of plastidial pyruvate kinases in seeds of Arabidopsis thaliana,THE PLANT JOURNAL, Issue 3 2007Sébastien Baud Summary Pyruvate kinase (PK) catalyses the irreversible synthesis of pyruvate and ATP, which are both used in multiple biochemical pathways. These compounds are essential for sustained fatty acid production in the plastids of maturing Arabidopsis embryos. Using a real-time quantitative reverse transcriptase (RT)-PCR approach, the three genes encoding putative plastidial PKs (PKps) in Arabidopsis, namely PKp1 (At3g22960), PKp2 (At5g52920) and PKp3 (At1g32440), were shown to be ubiquitously expressed. However, only PKp1 and PKp2 exhibited significant expression in maturing seeds. The activity of PKp1 and PKp2 promoters was consistent with this pattern, and the study of the PKp1:GFP and PKp2:GFP fusion proteins confirmed the plastidial localization of these enzymes. To further investigate the function of these two PKp isoforms in seeds comprehensive functional analyses were carried out, including the cytological, biochemical and molecular characterization of two pkp1 and two pkp2 alleles, together with a pkp1pkp2 double mutant. The results obtained outlined the importance of these PKps for fatty acid synthesis and embryo development. Mutant seeds were depleted of oil, their fatty acid content was drastically modified, embryo elongation was retarded and, finally, seed germination was also affected. Together, these results provide interesting insights concerning the carbon fluxes leading to oil synthesis in maturing Arabidopsis seeds. The regulation of this metabolic network by the WRINKLED1 transcription factor is discussed, and emphasizes the role of plastidial metabolism and the importance of its tight regulation. [source] HYPOXIA-INDUCED ERYTHROPOIETIN PRODUCTION: A PARADIGM FOR OXYGEN-REGULATED GENE EXPRESSIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2006Christian Stockmann SUMMARY 1The mechanisms controlling the expression of the gene encoding for the hormone erythropoietin (EPO) are exemplary for oxygen-regulated gene expression. In humans and other mammals, hypoxia modulates EPO levels by increasing expression of the EPO gene. An association between polycythaemia and people living at high altitudes was first reported more than 100 years ago. 2Since the identification of EPO as the humoral regulator of red blood cell production and the cloning of the EPO gene, considerable progress has been made in understanding the regulation of EPO gene expression. This has finally led to the identification of a widespread cellular oxygen-sensing mechanism. Central to this mechanism is the transcription factor complex hypoxia-inducible factor (HIF)-1. 3The abundance and activity of HIF-1, a heterodimer of an ,- and ,-subunit, is predominantly regulated by oxygen-dependent post-translational hydroxylation of the ,-subunit. Non-heme ferrous iron containing hydroxylases use dioxygen and 2-oxoglutarate to specifically target proline and an asparagine residue in HIF-1,. As such, the three prolyl hydroxylases (prolyl hydroxylase domain-containing protein (PHD) 1, PHD2 and PHD3) and the asparagyl hydroxylase (factor inhibiting HIF (FIH)-1) act as cellular oxygen sensors. In addition to erythropoiesis, HIF-1 regulates a broad range of physiologically relevant genes involved in angiogenesis, apoptosis, vasomotor control and energy metabolism. Therefore, the HIF system is implicated in the pathophysiology of many human diseases. 4In addition to the tight regulation by oxygen tension, temporal and tissue-specific signals limit expression of the EPO gene primarily to the fetal liver and the adult kidney. [source] | |||||||||||||