Remodeling Epithelial Cell Organization: Transitions Between Front–Rear and Apical–Basal Polarity

Polarized epithelial cells have a distinctive apical–basal axis of polarity for vectorial transport of ions and solutes across the epithelium. In contrast, migratory mesenchymal cells have a front–rear axis of polarity. During development, mesenchymal cells convert to epithelia by coalescing into aggregates that undergo epithelial differentiation. Signaling networks and protein complexes comprising Rho family GTPases, polarity complexes (Crumbs, PAR, and Scribble), and their downstream effectors, including the cytoskeleton and the endocytic and exocytic vesicle trafficking pathways, together regulate the distributions of plasma membrane and cytoskeletal proteins between front–rear and apical–basal polarity. The challenge is to understand how these regulators and effectors are adapted to regulate symmetry breaking processes that generate cell polarities that are specialized for different cellular activities and functions.     

Interleukin-6 Mediates Epithelial–Stromal Interactions and Promotes Gastric Tumorigenesis

Interleukin-6 (IL-6) is a pleiotropic cytokine that affects various functions, including tumor development. Although the importance of IL-6 in gastric cancer has been documented in experimental and clinical studies, the mechanism by which IL-6 promotes gastric cancer remains unclear. In this study, we investigated the role of IL-6 in the epithelial–stromal interaction in gastric tumorigenesis. Immunohistochemical analysis of human gastritis, gastric adenoma, and gastric cancer tissues revealed that IL-6 was frequently detected in the stroma. IL-6–positive cells in the stroma showed positive staining for the fibroblast marker α-smooth muscle actin, suggesting that stromal fibroblasts produce IL-6. We compared IL-6 knockout (IL-6^−/−) mice with wild-type (WT) mice in a model of gastric tumorigenesis induced by the chemical carcinogen N-methyl-N-nitrosourea. The stromal fibroblasts expressed IL-6 in tumors from WT mice. Gastric tumorigenesis was attenuated in IL-6^−/− mice, compared with WT mice. Impaired tumor development in IL-6^−/− mice was correlated with the decreased activation of STAT3, a factor associated with gastric cancer cell proliferation. In vitro, when gastric cancer cell line was co-cultured with primary human gastric fibroblast, STAT3–related genes including COX-2 and iNOS were induced in gastric cancer cells and this response was attenuated with neutralizing anti-IL-6 receptor antibody. IL-6 production from fibroblasts was increased when fibroblasts were cultured in the presence of gastric cancer cell–conditioned media. IL-6 production from fibroblasts was suppressed by an interleukin-1 (IL-1) receptor antagonist and siRNA inhibition of IL-1α in the fibroblasts. IL-1α mRNA and protein were increased in fibroblast lysate, suggesting that cell-associated IL-1α in fibroblasts may be involved. Our results suggest the importance of IL-6 mediated stromal-epithelial cell interaction in gastric tumorigenesis.     

The Role of Gap Junctions in Endothelial–Stromal Cell Interactions

Human Physiology - Gap junctions are one of the most highly specialized intercellular communications providing not only electrical coupling but also metabolic cooperation between cells due to the...     

The Occurrence of Matriptase C-Terminal Fragments on the Apical and Basolateral Sides of Madin–Darby Canine Kidney Epithelial Cells

Matriptase is a type II transmembrane serine protease. In the present study, matriptase C-terminal fragments containing the catalytic serine protease domain were found to occur on the apical and basolateral sides of Madin–Darby canine kidney epithelial cells transfected with a cDNA encoding the protease. This suggests that matriptase interacts with various potential substrates when expressed in simple epithelia.     

Vegetation Pattern Formation Due to Interactions Between Water Availability and Toxicity in Plant–Soil Feedback

Development of a comprehensive theory of the formation of vegetation patterns is still in progress. A prevailing view is to treat water availability as the main causal factor for the emergence of vegetation patterns. While successful in capturing the occurrence of multiple vegetation patterns in arid and semiarid regions, this hypothesis fails to explain the presence of vegetation patterns in humid environments. We explore the rich structure of a toxicity-mediated model of the vegetation pattern formation. This model consists of three PDEs accounting for a dynamic balance between biomass, water, and toxic compounds. Different (ecologically feasible) regions of the model’s parameter space give rise to stable spatial vegetation patterns in Turing and non-Turing regimes. Strong negative feedback gives rise to dynamic spatial patterns that continuously move in space while retaining their stable topology.     

Molecular Bases of Cell–Cell Junctions Stability and Dynamics

Epithelial cell–cell junctions are formed by apical adherens junctions (AJs), which are composed of cadherin adhesion molecules interacting in a dynamic way with the cortical actin cytoskeleton. Regulation of cell–cell junction stability and dynamics is crucial to maintain tissue integrity and allow tissue remodeling throughout development. Actin filament turnover and organization are tightly controlled together with myosin-II activity to produce mechanical forces that drive the assembly, maintenance, and remodeling of AJs. In this review, we will discuss these three distinct stages in the lifespan of cell–cell junctions, using several developmental contexts, which illustrate how mechanical forces are generated and transmitted at junctions, and how they impact on the integrity and the remodeling of cell–cell junctions.Cell–cell junction formation and remodeling occur repeatedly throughout development. Epithelial cells are linked by apical adherens junctions (AJs) that rely on the cadherin-catenin-actin module. Cadherins, of which epithelial E-cadherin (E-cad) is the most studied, are Ca²⁺-dependent transmembrane adhesion proteins forming homophilic and heterophilic bonds in trans between adjacent cells. Cadherins and the actin cytoskeleton are mutually interdependent (Jaffe et al. 1990; Matsuzaki et al. 1990; Hirano et al. 1992; Oyama et al. 1994; Angres et al. 1996; Orsulic and Peifer 1996; Adams et al. 1998; Zhang et al. 2005; Pilot et al. 2006). This has long been attributed to direct physical interaction of E-cad with β-catenin (β-cat) and of α-catenin (α-cat) with actin filaments (for reviews, see Gumbiner 2005; Leckband and Prakasam 2006; Pokutta and Weis 2007). Recently, biochemical and protein dynamics analyses have shown that such a link may not exist and that instead, a constant shuttling of α-cat between cadherin/β-cat complexes and actin may be key to explain the dynamic aspect of cell–cell adhesion (Drees et al. 2005; Yamada et al. 2005). Regardless of the exact nature of this link, several studies show that AJs are indeed physically attached to actin and that cadherins transmit cortical forces exerted by junctional acto-myosin networks (Costa et al. 1998; Sako et al. 1998; Pettitt et al. 2003; Dawes-Hoang et al. 2005; Cavey et al. 2008; Martin et al. 2008; Rauzi et al. 2008). In addition, physical association depends in part on α-cat (Cavey et al. 2008) and additional intermediates have been proposed to represent alternative missing links (Abe and Takeichi 2008) (reviewed in Gates and Peifer 2005; Weis and Nelson 2006). Although further work is needed to address the molecular nature of cadherin/actin dynamic interactions, association with actin is crucial all throughout the lifespan of AJs. In this article, we will review our current understanding of the molecular mechanisms at work during three different developmental stages of AJs biology: assembly, stabilization, and remodeling, with special emphasis on the mechanical forces controlling AJs integrity and development.     

Interactions Between the Vegetative States of Phages λ and T1

Bacteria containing phage lambda in the vegetative state were produced either by induction of λ lysogens or by infection of sensitive cells with λ. These cells were superinfected with T1, and assayed for the production of λ, T1, or both. Although most of the cells produced only λ or T1, approximately 10% of the infectious centers were dual yielders. Examination of the progeny phage produced by the population of mixedly-infected cells showed that there was little, if any, phenotypic mixing, as determined by adsorption phenotype. T1am mutants in a variety of T1 genes were tested for their ability to exclude λ, but none were defective in this ability. One gene of T1, gene 4, can be complemented by λ.     

Glioma Cell Death: Cell–Cell Interactions and Signalling Networks

The prognosis for patients with malignant gliomas is poor, but improvements may emerge from a better understanding of the pathophysiology of glioma signalling. Recent therapeutic developments have implicated lipid signalling in glioma cell death. Stress signalling in glioma cell death involves mitochondria and endoplasmic reticulum. Lipid mediators also signal via extrinsic pathways in glioma cell proliferation, migration and interaction with endothelial and microglial cells. Glioma cell death and tumour regression have been reported using polyunsaturated fatty acids in animal models, human ex vivo explants, glioma cell preparations and in clinical case reports involving intratumoral infusion. Cell death signalling was associated with generation of reactive oxygen intermediates and mitochondrial and other signalling pathways. In this review, evidence for mitochondrial responses to stress signals, including polyunsaturated fatty acids, peroxidising agents and calcium is presented. Additionally, evidence for interaction of glioma cells with primary brain endothelial cells is described, modulating human glioma peroxidative signalling. Glioma responses to potential therapeutic agents should be analysed in systems reflecting tumour connectivity and CNS structural and functional integrity. Future insights may also be derived from studies of signalling in glioma-derived tumour stem cells.     

Oligodendrocyte–Neuron Interactions: Impact on Myelination and Brain Function

In the past, glial cells were considered to be ‘glue’ cells whose primary role was thought to be merely filling gaps in neural circuits. However, a growing number of reports have indicated the role of glial cells in higher brain function through their interaction with neurons. Myelin was originally thought to be just a sheath structure surrounding neuronal axons, but recently it has been shown that myelin exerts effects on the conduction velocity of neuronal axons even after myelin formation. Therefore, the investigation of glial cell properties and the neuron-glial interactions is important for understanding higher brain function. Moreover, since there are many neurological disorders caused by glial abnormalities, further understanding of glial cell-related diseases and the development of effective therapeutic strategies are warranted. In this review, we focused on oligodendrocyte-neuron interactions, with particular attention on (1) axonal signals underlying oligodendrocyte differentiation and myelination, (2) neuronal activity-dependent myelination and (3) the effects of myelination on higher brain function.

     

Epithelial–Mesenchymal Transition in Kidney Tubular Epithelial Cells Induced by Globotriaosylsphingosine and Globotriaosylceramide

Fabry disease is a lysosomal storage disorder caused by deficiency of alpha-galactosidase A (α-gal A), which results in the deposition of globotriaosylceramide (Gb3) in the vascular endothelium. Globotriaosylsphingosine (lyso-Gb3), a deacylated Gb3, is also increased in the plasma of patients with Fabry disease. Renal fibrosis is a key feature of advanced Fabry disease patients. Therefore, we evaluated the association of Gb3 and lyso-Gb3 accumulation and the epithelial–mesenchymal transition (EMT) on tubular epithelial cells of the kidney. In HK2 cells, exogenous treatments of Gb3 and lyso-Gb3 increased the expression of TGF-β, EMT markers (N-cadherin and α-SMA), and phosphorylation of PI3K/AKT, and decreased the expression of E-cadherin. Lyso-Gb3, rather than Gb3, strongly induced EMT in HK2 cells. In the mouse renal mesangial cell line, SV40 MES 13 cells, Gb3 strongly induced phenotype changes. The EMT induced by Gb3 was inhibited by enzyme α-gal A treatment, but EMT induced by lyso-Gb3 was not abrogated by enzyme treatment. However, TGF-β receptor inhibitor (TRI, SB525334) inhibited the activation of TGF-β and EMT markers in HK2 cells with Gb3 and lyso-Gb3 treatments. This study suggested that increased plasma lyso-Gb3 has a crucial role in the development of renal fibrosis through the cell-specific induction of the EMT in Fabry disease, and that TRI treatment, alongside enzyme replacement therapy, could be a potential therapeutic option for patients with Fabry disease.     

Physiological Responses of Zea mays Seedlings to Interactions Between Cadmium and Salinity

The effects of 0, 2.5, 5.0, and 10.0 pmol/L Cd^2＋（Cd（NO3）2.4H2O） and 0, 10, 25, 50, and 100 mmol/L NaCl on growth, photosynthesis and the content of some ions in maize （Zea mays L.） were investigated in the present study. With Increasing concentrations of Cd^2＋ or NaCI alone in Hoagland nutrient solution, the chlorophylls and starch content decreased. Combination treatment with salinity and cadmium increased the negative effects observed following the two stresses alone. Plants exhibiting growth retardation in response to one mild stress factor （25-50 mmol/L NaCl） became more tolerant to the other stress factor （Cd）. The exposure of plants to cadmium caused a partial reversal of the effects of salinity. Root and shoot growth, ion accumulation and levels of photosynthetic pigments were improved at moderate concentrations of the two stress factors Imposed jointly.     

Selenium–Mercury Interactions in Man and Animals

Selenium–mercury interactions were most extensively studied in relation to alleviation of Hg toxicity by added selenium. This presentation considers the influence of mercury on endogenous selenium, on its tissue and cellular “status” after lifelong or acute exposure to mercury vapor (Hg^o). Discussed are data obtained from (1) humans living near or working in a mercury mine, and (2) rats experimentally exposed in the mine. Mercury vapor is unique—or similar to methylmercury—because of its ability to penetrate cell membranes and so invade all cells, where it is oxidized in the biologically active form (Hg⁺⁺) by catalase. Such in situ-generated ions can react with endogenously generated highly reactive Se metabolites, like HSe−, and render a part of the selenium unavailable for selenoprotein synthesis. Data on human populations indicate that in moderate Hg exposure combined with an adequate selenium supply through diet, Se bioavailability can be preserved. On the other hand, the results of an acute exposure study emphasize the dual role of selenium in mercury detoxification. Besides the well-known Se coaccumulation through formation of nontoxic Hg–Se complexes, we observed noticeable Se (co)excretion, at least at the beginning of exposure. The higher Hg accumulation rate in the group of animals with lower basal selenium levels can also point to selenium involvement in mercury excretion. In such conditions there is a higher probability for decreased selenoprotein levels (synthesis) in some tissues or organs, depending on the synthesis hierarchy.     

Specific Interactions Between gC1qR and α1‐Adrenoceptor Subtypes

Abstract

The multi‐functional protein gC1qR has been reported to interact with an arginine‐rich motif in the C‐tail of hamster α_1B‐adrenoceptors (ARs), controlling their expression and subcellular localization. Since a similar motif is present in α_1D‐, but not α_1A‐ARs, we studied the specificity of this interaction. Human α₁‐ARs, tagged at their amino termini with Flag epitopes, were coexpressed in HEK293 cells with gC1qR containing a hemaglutinin (HA) tag at its carboxy terminus. Immunoprecipitation studies showed that Flag‐α_1B‐ or α_1D‐, but not α_1A‐ARs, caused coimmunoprecipitation of HA‐gC1qR, while immunoprecipitation of HA‐gC1qR caused coimmunoprecipitation of Flag‐α_1B‐ or α_1D‐, but not α_1A‐ARs, supporting specific interactions between subtypes. C‐terminal truncation of Flag‐α₁‐ARs prevented interaction with HA‐gC1qR, supporting previous conclusions about the role of the C‐terminal arginine‐rich motif. These studies suggest that gC1qR interacts specifically with α_1B‐ and α_1D‐, but not α_1A‐ARs, and this interaction depends on the presence of an intact C‐tail.     

Macrophage–Cryptococcus Interactions: An Update

Cryptococcus species are fungal pathogens that are a leading cause of mortality. Initial inoculation is through the pulmonary route and, if disseminated, results in severe invasive infection including meningoencephalitis. Macrophages are the dominant phagocytic cell that interacts with Cryptococcus. Emerging theories suggest that Cryptococcus microevolution in macrophages is linked to survival and virulence within the host. In addition, Cryptococcus elaborates virulence factors as well as usurps host machinery to establish macrophage activation states that are permissive to intracellular survival and replication. In this review, we provide an update of the recent findings pertaining to macrophage interaction with Cryptococcus and focus on new avenues for biomedical research.