Epithelial layers are integral for many physiological processes and are maintained by intercellular adhesive structures. During disease, these structures can disassemble, leading to breakdown of epithelia. TJs (tight junctions) are one type of intercellular adhesion. Loss of TJs has been linked to the pathogenesis of many diseases. The present review focuses on the role of vesicle trafficking in regulation of TJs, in particular trafficking of the TJ protein occludin. We examine how endocytosis and endosomal recycling modulate occludin localization under steady-state conditions and during stimulated TJ disassembly. ...
Tight junctions between epithelial and endothelial cells form selective barriers and paracellular channels and regulate paracellular transport of solutes, immune cells, and drugs. More specifically, tight junctions consist of proteins that laterally interconnect neighboring cells of epithelia and endothelia. Certain proteins seal the tight junction, so that a nearly impermeable barrier develops, whereas others form channels that allow for permeation between the cells. Recent investigations have focused on tight junction proteins, belonging to the claudin family (claudins-1 to -27 in humans) and the newly defined group of TAMP (three proteins: occludin, Marvel-D2, and tricellulin). Barriers and Channels Formed by Tight Junction Proteins I showcases work in this area clustered around three major themes: the molecular properties of tight junctions, for example, the role of the claudin family of proteins and the formation of ion and charge-selective channels; the regulation of tight junction
In an attempt to clarify the complex nature of interactions between the cortical actin cytoskeleton and integral membrane proteins, recent studies brought into focus the ERM proteins, which serve as cross-linkers between specific plasma membrane proteins and cortical actin filaments. For ERM protein activation, specific signals, such as phosphorylation or binding of phosphatidylinositol 4,5-bisphosphate (lipid signaling molecule) to the N-terminal domain is required (8, 25, 36). Activation of ERM proteins may be triggered by physiological (14, 29) and pathophysiological (52, 58) processes. Ezrin is one of the host cytoskeletal proteins reorganized following EPEC infection (17). Here we examine the impact of this important enteric bacterial pathogen on ezrin activation and explore its involvement in EPEC pathogenesis.. In contrast to prototypic enteric bacterial pathogens, EPEC produces no recognized toxin and is essentially noninvasive. Instead, through a series of complex steps, EPEC intimately ...
TY - JOUR. T1 - Retinal pigment epithelial cells from dystrophic rats form normal tight junctions in vitro. AU - Chang, Chih Wei. AU - Defoe, Dennis M.. AU - Caldwell, Ruth B. PY - 1997/2/6. Y1 - 1997/2/6. N2 - Purpose. In the genetically defective Royal College of Surgeons (RCS) rat model for retinal degeneration, a breakdown occurs in the retinal pigment epithelial (RPE) cell tight junctions just as the photoreceptors begin to degenerate. These experiments sought to determine the impact of the RPE genetic defect on this alteration in the RPE cell tight junctions. Methods. Retinal pigment epithelial cell cultures prepared from RCS and control rats were treated with hormonally defined medium (HDM), base medium conditioned by RCS or control retinas, or unconditioned base medium. The tight junctions formed by these cultures were assayed functionally by measuring transepithelial electrical resistance and permeability. Junction structure was evaluated by immunolocalization of the tight junction ...
Aim of this volume is to clarify the relationship between molecular structure and function of tight junction proteins, as well as their regulation and their role in diseases. Current research may form a basis for future diagnostic and therapeutic approaches to diseases which seem to have not much in common but are characterized by defects of organ barriers, like Crohns disease, renal hypertension, inner ear deafness, and cancerous diseases. Topics include the functions of distinct tight junction proteins as barrier or channel formers for solutes and water, characteristics of the tight junction in inflammatory bowel diseases, posttranslational modifications of tight junction proteins, the relation between renal tight junction proteins and blood pressure control, and the molecular structure of claudin-claudin interactions NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit www.blackwellpublishing.com/nyas.
Characterization of the tight junction is proceeding rapidly and has stimulated advances in the fields of cell-cell interactions and epithelial cell biology. In addition to the list of proteins now found at the tight junction, we have learned that two previously characterized tight junction components, ZO-1 and ZO-2, are members of a larger protein family that appear to function in the organization of specific areas of the cell surface (11, 21, 23, 24, 27, 41, 44). Moreover, data suggest that some members of this family are involved in signal transduction and/or tumor suppression (1, 41, 46, 47), highlighting the importance of analyzing these molecules.. Here we present evidence of a novel member of the MAGUK family of proteins found at the tight junction. This 130-kD polypeptide, named ZO-3 because of homology to ZO-1 and ZO-2 (Figs. 5, Tables II and III) and localization at the tight junction (Figs. 7 and 8), contains 3 PDZ domains, an SH3 domain and a GUK region (Fig. 3). The arrangement of ...
In this study, we demonstrated (I) distinct expression patterns of five genes encoding for proteins involved in the formation of tight junctions in esophageal mucosa. In particular Claudin-1 in ERD and to lesser extent Claudin-2 was expressed at higher levels in patients with GERD. In contrast, ZO-1, ZO-2, and Occludin were not affected by the presence of GERD. (II) In general, altered gene expression of Claudin-1/-2 did not correlate with the degree of histomorphological changes in the esophageal mucosa of patients with GERD.. Tight junctions are composed of transmembrane proteins such as Occludin, 24 Claudins, several junctional adhesion molecules (JAMs) with different isoforms, E-Cadherin as well as cytosolic binding partners [43, 44]. The selection of the five genes studied was based on functional aspects. Occludin is critical for the formation of tight junctions in most tissues [45]. Claudin-1 is one of the numerous Claudins that seals intercellular space leading to higher barrier function ...
Tight junctions (TJs) are constructions indispensable to epithelial cells and are responsible for regulations of paracellular diffusion and maintenance of cellular polarity. interstitial tissues spaces. Located at the pinnacle of horizontal walls, TJs have both wall and barriers features. The barriers function represents a selectively permeable filtration system that adjusts paracellular diffusion of ions and solutes structured on charge and size, respectively (Gemstone, 1977 ). Barriers function is certainly firmly governed by a particular arranged of TJ protein, the claudins (Tsukita made up of a non-specific shRNA into MDCK II cells (brief hairpin non-specific control [shCtrl] cells). Specificities of RalA and RalB exhaustion had been ABT-263 decided by immunoblotting and immunofluorescence marking of endogenous protein; both RalB and RalA localised to the plasma membrane layer in subconfluent MDCK II cells, and this localization was untouched in shCtrl cells (Body 1B). In shRalA cells, ...
In mammalian epithelial cells, the most apical components of the lateral junctional complex are TJs that serve as intercellular barriers to regulate paracellular permeability and function as intramembranous fences to maintain the polarization of the apical and basolateral membrane domains ( Mitic and Anderson, 1998; Cereijido et al., 1998). A growing number of TJ-associated peripheral or integral proteins have been identified, and the characterized properties of these proteins provide a molecular basis for TJ formation and function. However, at present it is not fully understood how the formation of this complicated junctional structure is orchestrated in terms of the dynamic process.. We have previously identified ASIP, the mammalian homolog of C. elegans polarity protein PAR-3, as an epithelial TJ-associated peripheral protein ( Izumi et al., 1998); however, the physiological functions of mammalian ASIP/PAR-3 remain to be clarified. In this study, we provide two lines of evidence suggesting ...
Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was …
In the present study we identified a diverse group of Tcfap2c-regulated genes with established roles in blastocyst formation. These include genes that are important for TJ assembly (Cldn4, Cldn6, Tjp2, Tjp1), cell polarity (Pard6b) and fluid accumulation (Atp1b1, Aqp3). Claudin family members encode tetraspanin membrane proteins that serve crucial roles in TJ assembly and epithelial cell barrier function (Krause et al., 2008). In preimplantation embryos, disruption of Cldn4 and Cldn6 function via an inhibitory peptide impairs blastocyst development (Moriwaki et al., 2007). The TJ proteins Tjp1 and Tjp2 play an important role in connecting the actin skeleton with TJ complexes at the apical membrane (Schneeberger and Lynch, 2004). Embryos that lack Tjp1 or Tjp2 exhibit defects in blastocyst formation and/or undergo early embryonic lethality (Katsuno et al., 2008; Sheth et al., 2008). Likewise, in mouse preimplantation embryos the cell polarity regulator Pard6b is essential for blastocyst formation ...
in Journal of Biological Chemistry (2011), 286(19), 16879-90. Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen ... [more ▼]. Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase (GSK)-3beta inhibition independently induce the localization of epithelial tight junction components to the plasma membrane. The Ca(2+)-independent deposition of junctional proteins induced by AMPK activation and GSK-3beta inhibition is independent of E-cadherin. Furthermore, the nectin-afadin system is required for the deposition of tight junction components induced by AMPK activation, but it is not required for that induced by GSK-3beta inhibition. Phosphorylation studies demonstrate that afadin is ...
The tight junctions (TJ), which are located in the apical region between epithelial and endothelial cells, regulate the paracellular diffusion of ions and small molecules and play an important role in maintaining cell polarity, cell-cell integrity, and permeability. In the lung, epithelial cells are attached by TJ structures. They provide a permeable barrier and cell communication. The loss of barrier integrity, which is maintained by the expression of claudins (Cldn), results in cellular permibilization and leads to paracellular diffusion of solutes and harmful molecules. There are 27 known Cldn homologous members in mice and human. Cldn6 is mostly expressed in embryonic stem cells and associated with the programing of epithelial cells during embryo development and lung morphogenesis. In order to test the hypothesis that Cldn6 expression affects lung morphogenesis, we analyzed the expression pattern of Cldn6 during lung ontogenesis to examine cell-specific expression pattern of Cldn6 during each
The surface epithelium of newborn ferret airways matures rapidly in the first month of life. Prominent developmental features include a transition from predominantly non-ciliated to ciliated cells, quantitative and qualitative changes in secretion of macromolecules, and a transition from secretory to absorptive patterns of ion transport. Freeze-fracture replicas of ferret tracheal epithelium from 0 to 28 days of age exhibited progressive developmental patterns in tight junctional structure from beaded, unclosed patterns in newborns to more closed patterns at 28 days. Strand number increased while the depth of tight junctional structures and the proportion of strands exhibiting discontinuity decreased postnatally. Total transepithelial conductance, paracellular conductance, and cell size decreased over the first month. Our data suggest that changes in physiological parameters that reflect epithelial tight junction permeability can be attributed, at least in part, to maturation of this intercellular
This effect appeared to be mediated primarily by the action of HGF on the cytoplasmic membrane plaque protein ZO-1. ZO-1 is a peripheral membrane protein localized to the tight junction complex in epithelial and endothelial cells. Anchoring of ZO-1 with the underlying cytoskeleton is required for localization of occludin and claudin in the tight junction. ZO-1, -2, and -3 contain three PDZ domains, one SH3 domain, and one guanylyl kinase-like domain (GuK). Through its GuK domains, ZO-1 binds directly to the carboxyl termini of claudins and occludin and may function as an adaptor at the cytoplasmic surface of the tight junction to recruit other proteins, including cytoskeletal and signaling molecules. 4 These components can form a huge macromolecular complex at the cytoplasmic surface of tight junctions and may be involved in the regulation of endothelial and epithelial cell polarization, proliferation, and differentiation. 4 As an adaptor, ZO-1 is a critical regulatory protein between occludin ...
The glycosylphosphatidylinositol-anchored extracellular membrane serine protease prostasin is expressed in normal bladder urothelial cells. Bladder inflammation reduces prostasin expression and a loss of prostasin expression is associated with epithelial-mesenchymal transition (EMT) in human bladder transitional cell carcinomas. Non-steroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of various cancers including bladder cancer, but the molecular mechanisms underlying the anticancer effect of NSAIDs are not fully understood. The normal human bladder urothelial cell line UROtsa, the normal human trophoblast cell line B6Tert-1, human bladder transitional cell carcinoma cell lines UM-UC-5 and UM-UC-9, and the human breast cancer cell line JIMT-1 were used for the study. Expression changes of the serine proteases prostasin and matriptase, and cyclooxygenases (COX-1 and COX-2) in these cells following ibuprofen treatments were analyzed by means of reverse-transcription/quantitative polymerase
The intestinal epithelial layer serves as a barrier against pathogens and ingested toxins, which are present in the lumen of the intestine. The importance of the intestinal epithelial barrier is emphasized by the alterations in paracellular permeability and tight junction functions observed in inflammatory bowel disease (IBD) and colon cancer.
Extracellular Ca2+ triggers assembly and sealing of tight junctions (TJs) in MDCK cells. These events are modulated by G-proteins, phospholipase C, protein kinase C (PKC), and calmodulin. In the present work we observed that 1,2-dioctanoylglycerol (diC8) promotes the assembly of TJ in low extracellular Ca2+, as evidenced by translocation of the TJ-associated protein ZO-1 to the plasma membrane, formation of junctional fibrils observed in freeze-fracture replicas, decreased permeability of the intercellular space to [3H]mannitol, and reorganization of actin filaments to the cell periphery, visualized by fluorescence microscopy using rhodamine-phalloidin. In contrast, diC8 in low Ca2+ did not induce redistribution of the Ca-dependent adhesion protein E-cadherin (uvomorulin). Extracellular antibodies to E-cadherin block junction formation normally induced by adding Ca2+. diC8 counteracted this inhibition, suggesting that PKC may be in the signaling pathway activated by E-cadherin-mediated cell-cell ...
Earlier this month we launched a campaign to solicit peoples favourite PLOS Genetics issue images, published over the last ten years, from a selection of five. The winning image depicts claudin 1, E-cadherin and keratin 14 in the tail skin of a mouse and was featured as PLOS Genetics October 2014 issue image. Submitted by Tia DiTommaso et al, in their paper entitled Keratin 76 Is Required for Tight Junction Function and Maintenance of the Skin Barrier, this image depicts claudin 1 in green, E-cadherin in red and keratin 14 in blue, and the work highlights the role of Keratin 76 in wound repair and barrier activity in the skin. Find out more about the research behind the image in this post from the authors, published as part of our Understanding Images series. The image will be featured on the journals Twitter account and homepage during PLOS Genetics tenth anniversary week.. Thank you to all who voted!. Author: Jessica Miller, Publications Assistant, PLOS Genetics. ...
Inflammation caused by either intrinsic or extrinsic toxins results in intestinal barrier dysfunction, contributing to inflammatory bowel disease (IBD) and other diseases. Vitamin A is a widely used food supplement although its mechanistic effect on intestinal structures is largely unknown. The goal of this study was to explore the mechanism by investigating the influence of vitamin A on the intestinal barrier function, represented by tight junctions. IPEC-J2 cells were differentiated on transwell inserts and used as a model of intestinal barrier permeability. Transepithelial electrical resistance (TEER) was used as an indicator of monolayer integrity and paracellular permeability. Western blot and the reverse transcriptase-polymerase chain reaction were used to assess the protein and mRNA expression of tight junction proteins. Immunofluorescence microscopy was used to evaluate the localization and expression of tight junctions. Differentiated cells were treated with a vehicle control (Ctrl), ...
BACKGROUND: Intestinal epithelial barrier dysfunction, which involves myosin light chain kinase (MLCK) activation, contributes to the occurrence and progression of inflammation in inflammatory bowel disease (IBD). Wogonoside helps maintain intestinal homeostasis in mice with dextran sulfate sodium (DSS)-induced colitis, but it is unclear whether it modulates intestinal barrier function. PURPOSE: Here, we demonstrate that wogonoside protects against intestinal barrier dysfunction in colitis via the MLCK/pMLC2 pathway both in vivo and in vitro. METHODS: Caco-2 cell monolayers treated with the proinflammatory cytokine TNF-α showed barrier dysfunction and were assessed in the absence and presence of wogonoside for various physiological, morphological, and biochemical parameters. Colitis was induced by 3% DSS in mice, which were used as an animal model to explore the pharmacodynamics of wogonoside. We detected MLCK/pMLC2 pathway proteins via western blot analysis, assessed the cytokines IL-13 and ...
Izawa, Y., Gu, Y-H., Osada, T., Kanazawa, M., Hawkins, B., Koziol, J., ... del Zoppo, G. (2017). β1-integrin-matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability. Journal of Cerebral Blood Flow and Metabolism. DOI: 10.1177/0271678X17722108 ...
Mouse monoclonal ZO1 tight junction protein antibody [mAbcam 61357] validated for WB, IP, Flow Cyt and tested in Human. Referenced in 2 publications and 5…
Cingulin is specifically localized at tight junctions in epithelial cells, unlike ZO-1, which is also detected at adherens-type junctions in non-epithelial cells ... development, cingulin is detected at a cortical localization, and then accumulates at apical junctions, unlike ZO-1 and other junctional proteins, that are targeted to the new regions ... Cingulin interacts with ZO-1 and several other tight junction proteins, in addition to interacting with actin and myosin ...
Purpose: : To investigate the formation of the tight junction of endothelial cells in the capillary of developing rat retina. Methods: : The rat retinas were immunostained with monoclonal antisera against zonular occludensa 1 (ZO-1) (1:1,000 Zymed) and occludin (1:250, Zymed), markers of the tight junction between endothelial cells, at postnatal day (P) 7, 9, 10, 11, 14 and 49. For guiding the retinal blood vessels, polyclonal antisera against α-smooth muscle actin (1:1,000, Sigma), a pericyte marker, was used. Results: : From P7, the endothelial cells in the ganglion cell layer (GCL) expressed ZO-1 immunoreactivity. But, the endothelial cells in the outer plexiform layer (OPL) began to express ZO-1 immunoreactivity from P10. The expression of ZO-1 was consistent with the time of formation of retinal capillaries. Occludin immunoreactivity was visible in the endothelial cells of the GCL and OPL around P10, although a few occludin immunoreactive endothelial cells occurred in the GCL of the ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The TJP2 protein (Tight Junction Protein 2, sometimes called ZO2) plays a role in "tight junctions". Tight junctions are areas where the membranes of two adjacent cells join to form a barrier. The barrier controls what molecules are able to pass between cells. Such junctions are important throughout the body, and TJP2 is not specific to the liver. A mild form of liver disease associated with mutations in the TPJ 2 gene was previously called familial hypercholanaemia (which means high bile salts in blood). Only a small number of patients with PFIC caused by TJP2 mutation have been studied so far, so it is not yet understood of what manifestations, other than liver disease and its consequences that TJP2 deficiency patients may have.. ...
Epithelial and endothelial cells form the external lining of outer and inner body surfaces and blood vessels of multicellular organisms. Thus, they create separate compartments each exhibiting an environment optimally adjusted to their respective function. To build up such compartments epithelial and endothelial cells have to restrict the paracellular diffusion of substances. The paracellular cleft is sealed by tight junctions (TJ). In electron microscopical images TJs appear as a network of intermembranous strands in the apical region of the lateral cell membrane of epithelial and endothelial cells. Claudins (Cld) form the structural backbone of TJs. The present study provided evidence for the first time that single amino acids of the second extracellular loop (ECL) of a claudin are essential for the paracellular tightness of epithelial cells. The effect of single amino acid substitutions of the second ECL of Cld5 were studied in cells expressing various other endogenous claudins except Cld5. ...
Biological barriers are indispensable for the integrity and function of many vertebrate organs. The barrier function is based on intercellular protein complexes of the plasma membrane which form paracellular diffusion barriers and separate internal and external fluid compartments, an indispensable prerequisite for every organ development and function. The review summarizes key characteristics and molecular structure of intercellular junctions (tight junctions and adherens junctions) responsible for cellular barrier formation. One of the most important such cellular barriers is the blood-brain barrier (BBB) which forms an active interface between the circulation and neural tissue. Its principal cellular components are cerebral endothelial cells, pericytes and astrocytes, whose finely tuned interactions are needed for a proper function. The review highlights the most important functions of the BBB including some novel regulatory aspects as well.. ...
Identify an antibody against an adhesion junction protein that is commercially available. Add a link to the original data sheet page and identify the type of adhesion junction. Include the following information: type of antibody (polyclonal, monoclonal), species raised in, species reacts against, types of application uses, and if available any reference using that antibody. Tight Junction Protein 1 Antibody Original Data Sheer for Tight Junction Protein 1 Antibody Type of adhesion junction: human zona occludens 1, specifically ZO-1 alpha-minus found both in endothelial cells and the highly specialized epithelial junctions of renal glomeruli and Sertoli cells of the seminiferous tubules. Type of antibody: Polyclonal Species raised in: Guinea Pig Species reactivity: Human, Mouse, Rat, and Canine Types of application uses: Immunohistology, immunofluorescence and Western blotting References that uses this antibody: 1. ,pubmed,22314269,/pubmed,[3] 2. ,pubmed,22162948,/pubmed,[4] ...
Identify an antibody against an adhesion junction protein that is commercially available. Add a link to the original data sheet page and identify the type of adhesion junction. Include the following information: type of antibody (polyclonal, monoclonal), species raised in, species reacts against, types of application uses, and if available any reference using that antibody. Tight Junction Protein 1 Antibody Original Data Sheer for Tight Junction Protein 1 Antibody Type of adhesion junction: human zona occludens 1, specifically ZO-1 alpha-minus found both in endothelial cells and the highly specialized epithelial junctions of renal glomeruli and Sertoli cells of the seminiferous tubules. Type of antibody: Polyclonal Species raised in: Guinea Pig Species reactivity: Human, Mouse, Rat, and Canine Types of application uses: Immunohistology, immunofluorescence and Western blotting References that uses this antibody: 1. ,pubmed,22314269,/pubmed,[3] 2. ,pubmed,22162948,/pubmed,[4] ...
Tight junctions are one mode of cell-cell adhesion in epithelial and endothelial cellular sheets. They act as a primary barrier to the diffusion of solutes through the intercellular space, create a boundary between the apical and the basolateral plasma membrane domains, and recruit various cytoskele …
Reaktivität: Hund, Human, Maus and more. 60 verschiedene TJP3 Antikörper vergleichen. Alle direkt auf antikörper-online bestellbar!
Adapter protein involved in asymmetrical cell division and cell polarization processes. Probably involved in the formation of epithelial tight junctions. Association with PARD3 may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (PubMed:15761148). Regulates centrosome organization and function. Essential for the centrosomal recruitment of key proteins that control centrosomal microtubule organization (By similarity).
The precise regulation of intestinal epithelial TJs is crucial to maintaining barrier function between the luminal milieu and the internal environment. Recent studies have revealed an important role for Rho GTPases in regulating TJ structure/function (22, 29). In particular, TJ strand organization has been shown to be altered by constitutively active RhoA and Rac1 mutants (22) and inactivation of GTPases by C. difficile toxins is known to cause redistribution of occludin and ZO-1 from membrane microdomains or membrane rafts (32). As a result, we have further explored the mechanisms whereby paracellular permeability is influenced by this family of mediators and investigated whether the inactivation of a single GTPase (RhoA, Rac1, or Cdc42) has an effect on TJ distribution in such membrane rafts and whether TJ proteins involved in strand formation (such as claudin-1 and -2) are altered in this setting.. Using MDCK cell lines that express constitutively active or dominant-negative RhoA, Rac1, or ...
Steed, Emily, Elbediwy, Ahmed, Vacca, Barbara, Dupasquier, Sebastien, Hemkemeyer, Sandra A., Suddason, Tesha, Costa, Ana C., Beaudry, Jean-Bernard, Zihni, Ceniz, Gallagher, Ewen, Pierreux, Christophe E., Balda, Maria S. and Matter, Karl (2014) MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival. Journal of Cell Biology, 204(5), pp. 821-838. ISSN (print) 0021-9525 ...
When DArcy Wentworth Thompsons On Growth and Form was published 100 years ago, it raised the question of how biological forms arise during development and across evolution. In light of the advances in molecular and cellular biology since then, a succinct modern view of the question states: how do genes encode geometry? Our new special issue is packed with articles that use mathematical and physical approaches to gain insights into cell and tissue patterning, morphogenesis and dynamics, and that provide a physical framework to capture these processes operating across scales.. Read the Editorial by guest editors Thomas Lecuit and L. Mahadevan, as they provide a perspective on the influence of DArcy Thompsons work and an overview of the articles in this issue.. ...
The nonsense-mediated mRNA decay (NMD) pathway is a cellular quality control and post-transcriptional gene regulatory mechanism and is essential for viability in most multicellular organisms. A complex of proteins has been identified to be required for NMD function to occur, however there is an incomplete understanding of the individual contributions of each of these factors to the NMD process. Central to the NMD process are three proteins, Upf1 (SMG-2), Upf2 (SMG-3), and Upf3 (SMG-4), which are found in all eukaryotes, with Upf1 and Upf2 being absolutely required for NMD in all organisms in which their functions have been examined. The other known NMD factors, Smg1, Smg5, Smg6, and Smg7 are more variable in their presence in different orders of organisms and are thought to have a more regulatory role. Here we present the first genetic analysis of the NMD factor Smg5 in Drosophila. Surprisingly, we find that unlike the other analyzed Smg genes in this organism, Smg5 is essential for NMD ...
The Trans-Epithelial Permeability (TEP) Assay, is a cell-based assay used to evaluate the potential ocular irritancy of test chemicals by measuring the permeability of sodium fluorescein (or fluorescein leakage) through a confluent monolayer of Madin-Darby Canine Kidney (MDCK) cells. The MDCK cell line is used since it forms tight junctions in a confluent monolayer similar to those formed in the outermost corneal and conjunctival epithelial layers. The disruption of the tight junctions by chemicals is one of the early events typical... Trans-Epithial Permeability ...
Epithelial to mesenchymal transition (EMT) and the reciprocal mesenchymal to epithelial transition (MET) are key processes involved in both tumor metastasis and development. During EMT, epithelial cells lose their plasma membrane polarities, break their intercellular tight junctions, and degrade basement membrane extracellular matrix components to become migratory mesenchymal cells. MET is a common process during organogenesis, when migrating stem cells will begin to express genes important for tight junctions, as well as other genes important for stationary epithelial cells. Cell surface receptor, extracellular matrix, and cytoskeletal genes mediating cell adhesion, migration, and morphogenesis are all central to EMT. Tumor cells migrate to distal tissues via uncontrolled EMT, a common result during the oncogenic process. Analysis of EMT and MET mechanisms may yield new insights into their regulation during oncogenesis, providing novel drug targets ...
Two essential features of the RPE are its polarity and barrier properties. The RPE is polarized, because it separates the neural retina from the fenestrated capillaries in the choroid. The apical membrane of RPE interacts with the photoreceptors; the basal membrane interacts with the choroid. Like other epithelia, the apical and basolateral membranes have different protein compositions that enable each to interact with different environments. The barrier properties are regulated by two components. Transepithelial transport through the cells is regulated by plasma membrane pumps and transporters. Passive diffusion through the paracellular spaces is regulated by the strands of tight junctions that encircle each cell. Tight junctions are semi-selective, which means some solutes cross them more readily than others. By regulating both the transcellular and paracellular pathways, the RPE regulates the ionic composition of the subretinal space. For review see: Wilt SD, Rizzolo LJ: Unique aspects of the ...
Two essential features of the RPE are its polarity and barrier properties. The RPE is polarized, because it separates the neural retina from the fenestrated capillaries in the choroid. The apical membrane of RPE interacts with the photoreceptors; the basal membrane interacts with the choroid. Like other epithelia, the apical and basolateral membranes have different protein compositions that enable each to interact with different environments. The barrier properties are regulated by two components. Transepithelial transport through the cells is regulated by plasma membrane pumps and transporters. Passive diffusion through the paracellular spaces is regulated by the strands of tight junctions that encircle each cell. Tight junctions are semi-selective, which means some solutes cross them more readily than others. By regulating both the transcellular and paracellular pathways, the RPE regulates the ionic composition of the subretinal space. For review see: Wilt SD, Rizzolo LJ: Unique aspects of the ...
E-cadherin-mediated cell-cell interactions in the zonula adherens play an important role in the formation of the intercellular tight junctions found in the blood-brain barrier. However, it is also responsible for the low permeation of drugs into the brain. In this study, HAV6 peptide derived from the EC1 domain of E-cadherin was found to enhance the permeation of 14C-mannitol and [3H(G)]-daunomycin through the blood brain barrier of the in situ rat brain perfusion model. In addition, HAV6 peptide and verapamil have a synergistic effect in enhancing the BBB permeation of daunomycin. A new intercellular-junction resealing assay was also developed using Caco-2 monolayers to evaluate new peptides (BLG2, BLG3, and BLG4) derived from the bulge regions of the EC2, EC3, and EC4 domains of E-cadherin. BLG2 and BLG4 peptides but not BLG3 peptides were found to be effective in blocking the resealing of the intercellular junctions. The positive control peptides (ADT10, ADT6, and HAV10) block the resealing ...
For every experimental group, brains from at minimum 3 distinct litter had been analyzed and when compared to the in accordance NaCl handle group. qPCR approach improvement exposed that only samples must be when compared to every other which have gone through experimental treatment, mind isolation, storage, purification and evaluation preparing steps with each other. Therefore, for every DEX-treatment the according NaCl handle group was carried out at the exact same time. In addition, owing to the large complete variety of samples, but limited sample variety which could be purified at the same time, only samples from mice at the same age and identical variety of antenatal injections ended up compared to every other by using a two-tailed Student`s t-take a look at. Data are offered as the signifies ± SEM. The major tight junction molecule and mind endothelial mobile marker claudin-five was investigated originally. Triple maternal DEX remedy drastically decreased claudin-5 mRNA expression to .54 ...
It is well known that this reagent leads to a depletion of extracellular Ca2+ which in turn causes a disassembly of tight junction [1, 2]. The latter is reflected by a significant drop in the TER readings. Subsequent replacement of the EGTA containing medium by standard medium led to a regeneration of the tight junctions network as revealed by increasing TER readings. For validation of the temporary break down of the barrier function two cell cultures were fixed just before removal of EGTA. Samples were then stained for immunofluorescent analysis of cell nuclei and ZO-1 proteins. Imaging by Confocal Laser Scanning Microscopy and comparison with the untreated reference cell culture clearly revealed the disintegration of the tight junctions network induced by EGTA exposure. These findings are in excellent agreement with the TER results and demonstrate the benefits of using a label-free and noninvasive technique as implemented in the cellZscope.. Cell layer formation. Application of impedance ...
The C\terminal fragment of enterotoxin (C\CPE) modulates the tight junction protein claudin and disturbs the tight junctional barrier. epithelial cells (HPDEs) had been treated with C\CPE 194 and C\CPE meters19. In well\differentiated cells of the pancreatic malignancy cell collection HPAC, C\CPE 194 and C\CPE meters19 interrupted both the hurdle and fencing features without adjustments in manifestation of claudin\1 and \4, collectively with an boost of MAPK phosphorylation. C\CPE 194, but not really C\CPE meters19, improved the cytotoxicity of the anticancer brokers gemcitabine and H\1. In differentiated pancreatic malignancy cell collection PANC\1 badly, C\CPE 194, but not really C\CPE meters19, reduced claudin\4 phrase and improved MAPK activity and the cytotoxicity of the anticancer agencies. In regular HPDEs, C\CPE 194 and C\CPE meters19 reduced claudin\4 phrase and improved the MAPK activity, whereas they do not really influence the cytotoxicity of the anticancer agencies. Our results ...
All of us in the business talk about the blood-brain barrier, but. . .no, Im not going to end this sentence with . . .none of us do anything about it,
1. What is the distance between the points (1, 4) and (4, 8)? I said Distance = 5 2. Find the slope between (1, 4) and (4, 8) I said 4/3 3. Are the expressions (4x+4)/4 and x+1 equivalent? I said Yes 4. Simplify (x+y)2 x2 + 2xy + y2 5. Is (x - y )2 = x2 - y2? No. It is ... ...
Membrane Protein Structure and Function, Antioxidant Vitamins, ESR Spectroscopy, Fluorescence Spectroscopy,Membrane,Protein Structure,Spectroscopy. ...
My research focus in the Harrison lab is on studying the role of reactive oxygen species in vascular function especially in the setting of hypertension and cardiovascular disease. ...