Mouse adenovirus type 1-induced breakdown of the blood-brain barrier.
AuthorsGralinski LE, Ashley SL, Dixon SD, Spindler KR,
JournalJ Virol
PubMed ID19570856
Infection with mouse adenovirus type 1 (MAV-1) results in fatal acute encephalomyelitis in susceptible mouse strains via infection of brain endothelial cells. Wild-type (wt) MAV-1 causes less brain inflammation than an early region 3 (E3) null virus in C57BL/6 mice. A mouse brain microvascular endothelial cell line infected with wt ... More
The keratin-binding protein Albatross regulates polarization of epithelial cells.
AuthorsSugimoto M, Inoko A, Shiromizu T, Nakayama M, Zou P, Yonemura S, Hayashi Y, Izawa I, Sasoh M, Uji Y, Kaibuchi K, Kiyono T, Inagaki M,
JournalJ Cell Biol
PubMed ID18838552
'The keratin intermediate filament network is abundant in epithelial cells, but its function in the establishment and maintenance of cell polarity is unclear. Here, we show that Albatross complexes with Par3 to regulate formation of the apical junctional complex (AJC) and maintain lateral membrane identity. In nonpolarized epithelial cells, Albatross ... More
Growth-factor receptor-bound protein-2 (Grb2) signaling in B cells controls lymphoid follicle organization and germinal center reaction.
AuthorsJang IK, Cronshaw DG, Xie LK, Fang G, Zhang J, Oh H, Fu YX, Gu H, Zou Y
JournalProc Natl Acad Sci U S A
PubMed ID21508326
'Grb2 (growth-factor receptor-bound protein-2) is a signaling adaptor that interacts with numerous receptors and intracellular signaling molecules. However, its role in B-cell development and function remains unknown. Here we show that ablation of Grb2 in B cells results in enhanced B-cell receptor signaling; however, mutant B cells do not form ... More
CD44 regulates tight-junction assembly and barrier function.
AuthorsKirschner N, Haftek M, Niessen CM, Behne MJ, Furuse M, Moll I, Brandner JM,
JournalJ Invest Dermatol
PubMed ID21191420
'Upon barrier disturbance, adult CD44 knockout (KO) mice show delayed recovery of epidermal barrier function. This correlates with the loss of apical polarization of lamellar body (LB) secretion. As tight junctions (TJs) are crucial for barrier function and regulate polarized targeting of vesicles, we hypothesized that CD44 regulates TJs and ... More
Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation.
'Claudins are a family of integral membrane proteins of the tight junction that are thought to participate in the permeation of solutes across epithelia via the paracellular pathway. Claudin-8 is expressed in the distal renal tubule, which has a characteristically low passive permeability to monovalent cations. To test the hypothesis ... More
Trafficking of cholera toxin-ganglioside GM1 complex into Golgi and induction of toxicity depend on actin cytoskeleton.
AuthorsBadizadegan K, Wheeler HE, Fujinaga Y, Lencer WI,
JournalAm J Physiol Cell Physiol
PubMed ID15294854
'Intestinal epithelial lipid rafts contain ganglioside GM1 that is the receptor for cholera toxin (CT). The ganglioside binds CT at the plasma membrane (PM) and carries the toxin through the trans-Golgi network (TGN) to the endoplasmic reticulum (ER). In the ER, a portion of the toxin unfolds and translocates to ... More
Differences in claudin synthesis in primary cultures of acinar cells from rat salivary gland are correlated with the specific three-dimensional organization of the cells.
'Tight junctions are essential for the maintenance of epithelial cell polarity. We have previously established a system for the primary culture of salivary parotid acinar cells that retain their ability to generate new secretory granules and to secrete proteins in a signal-dependent manner. Because cell polarity and cell-cell adhesion are ... More
Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis.
AuthorsBreiderhoff T, Himmerkus N, Stuiver M, Mutig K, Will C, Meij IC, Bachmann S, Bleich M, Willnow TE, Müller D,
JournalProc Natl Acad Sci U S A
PubMed ID22891322
'In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle''s loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates ... More
E-cadherin differentially regulates the assembly of Connexin43 and Connexin32 into gap junctions in human squamous carcinoma cells.
AuthorsChakraborty S, Mitra S, Falk MM, Caplan SH, Wheelock MJ, Johnson KR, Mehta PP
JournalJ Biol Chem
PubMed ID20086013
'It is as yet unknown how the assembly of connexins (Cx) into gap junctions (GJ) is initiated upon cell-cell contact. We investigated whether the trafficking and assembly of Cx43 and Cx32 into GJs were contingent upon cell-cell adhesion mediated by E-cadherin. We also examined the role of the carboxyl termini ... More
Calcium dobesilate inhibits the alterations in tight junction proteins and leukocyte adhesion to retinal endothelial cells induced by diabetes.
AuthorsLeal EC, Martins J, Voabil P, Liberal J, Chiavaroli C, Bauer J, Cunha-Vaz J, Ambrósio AF
JournalDiabetes
PubMed ID20627932
'Calcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy in the last decades, but its mechanisms of action are not elucidated. CaD is able to correct the excessive vascular permeability in the retina of diabetic patients and in experimental diabetes. We investigated the molecular and cellular mechanisms ... More
The occludin and ZO-1 complex, defined by small angle X-ray scattering and NMR, has implications for modulating tight junction permeability.
AuthorsTash BR, Bewley MC, Russo M, Keil JM, Griffin KA, Sundstrom JM, Antonetti DA, Tian F, Flanagan JM,
JournalProc Natl Acad Sci U S A
PubMed ID22711802
'Tight junctions (TJs) are dynamic cellular structures that are critical for compartmentalizing environments within tissues and regulating transport of small molecules, ions, and fluids. Phosphorylation-dependent binding of the transmembrane protein occludin to the structural organizing protein ZO-1 contributes to the regulation of barrier properties; however, the details of their interaction ... More
Impact of intra- and interspecies variation of occludin on its function as coreceptor for authentic hepatitis C virus particles.
AuthorsCiesek S, Westhaus S, Wicht M, Wappler I, Henschen S, Sarrazin C, Hamdi N, Abdelaziz AI, Strassburg CP, Wedemeyer H, Manns MP, Pietschmann T, von Hahn T,
JournalJ Virol
PubMed ID21632765
Hepatitis C virus (HCV) is characterized by a narrow host range and high interindividual variability in the clinical course of infection. Both of these traits are thought to be largely due to genetic variation between species and between individual hosts. The tight junction component occludin (OCLN) is essential for HCV ... More
Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells.
AuthorsAmasheh S, Meiri N, Gitter AH, Schöneberg T, Mankertz J, Schulzke JD, Fromm M,
JournalJ Cell Sci
PubMed ID12432083
Tight junctions seal the paracellular pathway of epithelia but, in leaky tissues, also exhibit specific permeability. In order to characterize the contribution of claudin-2 to barrier and permeability properties of the tight junction in detail, we studied two strains of Madin-Darby canine kidney cells (MDCK-C7 and MDCK-C11) with different tight ... More
Ochratoxin A increases permeability through tight junctions by removal of specific claudin isoforms.
AuthorsMcLaughlin J, Padfield PJ, Burt JP, O'Neill CA,
JournalAm J Physiol Cell Physiol
PubMed ID15229101
On interaction with the intestine, the mycotoxin ochratoxin A is know to cause rapid inflammation, diarrhea, and increased bacterial translocation. All these effects are consistent with a decrease in epithelial barrier function. However, this has not been shown directly. We determined that ochratoxin A is able to reduce the barrier ... More
Hypoxia increases transepithelial electrical conductance and reduces occludin at the plasma membrane in alveolar epithelial cells via PKC-? and PP2A pathway.
During pulmonary edema, the alveolar space is exposed to a hypoxic environment. The integrity of the alveolar epithelial barrier is required for the reabsorption of alveolar fluid. Tight junctions (TJ) maintain the integrity of this barrier. We set out to determine whether hypoxia creates a dysfunctional alveolar epithelial barrier, evidenced ... More
Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain.
AuthorsMullier A, Bouret SG, Prevot V, Dehouck B,
JournalJ Comp Neurol
PubMed ID20127760
The median eminence is one of the seven so-called circumventricular organs. It is located in the basal hypothalamus, ventral to the third ventricle and adjacent to the arcuate nucleus. This structure characteristically contains a rich capillary plexus and features a fenestrated endothelium, making it a direct target of blood-borne molecules. ... More
Claudin extracellular domains determine paracellular charge selectivity and resistance but not tight junction fibril architecture.
AuthorsColegio OR, Van Itallie C, Rahner C, Anderson JM,
JournalAm J Physiol Cell Physiol
PubMed ID12700140
Tight junctions (TJs) regulate paracellular permeability across epithelia and vary widely in their transepithelial electrical resistance (TER) and charge selectivity. The claudin family of transmembrane proteins influences these properties. We previously reported that claudin-4 increased TER approximately 300% when expressed in low-resistance Madin-Darby canine kidney (MDCK) II cells and decreased ... More
Effects of proinflammatory cytokines on the claudin-19 rich tight junctions of human retinal pigment epithelium.
AuthorsPeng S, Gan G, Rao VS, Adelman RA, Rizzolo LJ,
JournalInvest Ophthalmol Vis Sci
PubMed ID22761260
Chronic, subclinical inflammation contributes to the pathogenesis of several ocular diseases, including age-related macular degeneration. Proinflammatory cytokines affect tight junctions in epithelia that lack claudin-19, but in the retinal pigment epithelium claudin-19 predominates. We examined the effects of cytokines on the tight junctions of human fetal RPE (hfRPE). hfRPE was ... More
Paracellular Cl- permeability is regulated by WNK4 kinase: insight into normal physiology and hypertension.
AuthorsKahle KT, Macgregor GG, Wilson FH, Van Hoek AN, Brown D, Ardito T, Kashgarian M, Giebisch G, Hebert SC, Boulpaep EL, Lifton RP,
JournalProc Natl Acad Sci U S A
PubMed ID15465913
Paracellular ion flux across epithelia occurs through selective and regulated pores in tight junctions; this process is poorly understood. Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension and hyperkalemia. Whereas WNK4 is known to regulate several transcellular transporters and channels involved in NaCl and ... More
Cultured monolayers of the dog jejunum with the structural and functional properties resembling the normal epithelium.
AuthorsWeng XH, Beyenbach KW, Quaroni A,
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID15550553
The development of a culture of the normal mammalian jejunum motivated this work. Isolated crypt cells of the dog jejunum were induced to form primary cultures on Snapwell filters. Up to seven subcultures were studied under the electron microscope and in Ussing chambers. Epithelial markers were identified by RT-PCR, Western ... More
Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex.
AuthorsNunbhakdi-Craig V, Machleidt T, Ogris E, Bellotto D, White CL, Sontag E
JournalJ Cell Biol
PubMed ID12196510
Tight junctions (TJs) play a crucial role in the establishment of cell polarity and regulation of paracellular permeability in epithelia. Here, we show that upon calcium-induced junction biogenesis in Madin-Darby canine kidney cells, ABalphaC, a major protein phosphatase (PP)2A holoenzyme, is recruited to the apical membrane where it interacts with ... More
Protein kinase C? phosphorylates occludin and promotes assembly of epithelial tight junctions.
AuthorsJain S, Suzuki T, Seth A, Samak G, Rao R
JournalBiochem J
PubMed ID21545357
Protein kinases play an important role in the regulation of epithelial tight junctions. In the present study, we investigated the role of PKC? (protein kinase C?) in tight junction regulation in Caco-2 and MDCK (Madin-Darby canine kidney) cell monolayers. Inhibition of PKC? by a specific PKC? pseudosubstrate peptide results in ... More
Functional ESCRT machinery is required for constitutive recycling of claudin-1 and maintenance of polarity in vertebrate epithelial cells.
AuthorsDukes JD, Fish L, Richardson JD, Blaikley E, Burns S, Caunt CJ, Chalmers AD, Whitley P
JournalMol Biol Cell
PubMed ID21757541
Genetic screens in Drosophila have identified regulators of endocytic trafficking as neoplastic tumor suppressor genes. For example, Drosophila endosomal sorting complex required for transport (ESCRT) mutants lose epithelial polarity and show increased cell proliferation, suggesting that ESCRT proteins could function as tumor suppressors. In this study, we show for the ... More
Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo.
AuthorsShifflett DE, Clayburgh DR, Koutsouris A, Turner JR, Hecht GA
JournalLab Invest
PubMed ID16127426
Enteropathogenic Escherichia coli (EPEC) infection disrupts tight junctions (TJs) and perturbs intestinal barrier function in vitro. E. coli secreted protein F (EspF) is, in large part, responsible for these physiological and morphological alterations. We recently reported that the C57BL/6J mouse is a valid in vivo model of EPEC infection as ... More