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
Altered expression of junctional adhesion molecule 4 in injured podocytes.
AuthorsHarita Y, Miyauchi N, Karasawa T, Suzuki K, Han GD, Koike H, Igarashi T, Shimizu F, Kawachi H,
JournalAm J Physiol Renal Physiol
PubMed ID16118391
'Recent investigations have revealed the importance of glomerular podocytes with its diaphragm as the major filtration barrier. Junctional adhesion molecule 4 (JAM4) has been identified as a protein that interacts with membrane-associated guanyl kinase inverted (MAGI)-1 and is reported to be expressed on podocytes. To elucidate the role of JAM4 ... More
Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast.
AuthorsKominsky SL, Argani P, Korz D, Evron E, Raman V, Garrett E, Rein A, Sauter G, Kallioniemi OP, Sukumar S,
JournalOncogene
PubMed ID12673207
'Claudins are transmembrane proteins that seal tight junctions, and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Here, we report that Claudin-7 (CLDN-7) expression is lower in invasive ductal carcinomas (IDC) of the breast than in normal breast epithelium, ... 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
Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion.
AuthorsLu Z, Ghosh S, Wang Z, Hunter T,
JournalCancer Cell
PubMed ID14706341
'EGF receptor (EGFR) overexpression correlates with metastasis in a variety of carcinomas, but the underlying mechanisms are poorly understood. We demonstrated that EGF disrupted cell-cell adhesion and caused epithelial-to-mesenchymal transition (EMT) in human tumor cells overexpressing EGFR, and also induced caveolin-dependent endocytosis of E-cadherin, a cell-cell adhesion protein. Chronic EGF ... More
Neuronal connexin36 association with zonula occludens-1 protein (ZO-1) in mouse brain and interaction with the first PDZ domain of ZO-1.
AuthorsLi X, Olson C, Lu S, Kamasawa N, Yasumura T, Rash JE, Nagy JI,
JournalEur J Neurosci
PubMed ID15090040
'Among the 20 members in the connexin family of gap junction proteins, only connexin36 (Cx36) is firmly established to be expressed in neurons and to form electrical synapses at widely distributed interneuronal gap junctions in mammalian brain. Several connexins have recently been reported to interact with the PDZ domain-containing protein ... More
sPAR-3, a splicing variant of PAR-3, shows cellular localization and an expression pattern different from that of PAR-3 during enterocyte polarization.
'PAR-3 (partitioning-defective) is a scaffold-like PDZ (postsynaptic density-95/discs large/zonula occludens-1) domain-containing protein that forms a complex with PAR-6 and atypical PKC, localizes to tight junctions, and contributes to the formation of functional tight junctions. There are several alternatively spliced isoforms of PAR-3, although their physiological significance remains unknown. In this ... More
The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells.
AuthorsLopez C, Métral S, Eladari D, Drevensek S, Gane P, Chambrey R, Bennett V, Cartron JP, Le Van Kim C, Colin Y,
JournalJ Biol Chem
PubMed ID15611082
'RhBG is a nonerythroid member of the Rhesus (Rh) protein family, mainly expressed in the kidney and belonging to the Amt/Mep/Rh superfamily of ammonium transporters. The epithelial expression of renal RhBG is restricted to the basolateral membrane of the connecting tubule and collecting duct cells. We report here that sorting ... 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
Tight junction proteins expression and modulation in immune cells and multiple sclerosis.
AuthorsMandel I, Paperna T, Glass-Marmor L, Volkowich A, Badarny S, Schwartz I, Vardi P, Koren I, Miller A,
JournalJ Cell Mol Med
PubMed ID21762372
'The tight junction proteins (TJPs) are major determinants of endothelial cells comprising physiological vascular barriers such as the blood-brain barrier, but little is known about their expression and role in immune cells. In this study we assessed TJP expression in human leukocyte subsets, their induction by immune activation and modulation ... More
Hailey-Hailey disease and tight junctions: Claudins 1 and 4 are regulated by ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 in cultured keratinocytes.
AuthorsRaiko L, Siljamäki E, Mahoney MG, Putaala H, Suominen E, Peltonen J, Peltonen S,
JournalExp Dermatol
PubMed ID22639968
'Mutations in the ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 cause Hailey-Hailey disease (HHD, OMIM 16960). HHD is characterized by epidermal acantholysis. We attempted to model HHD using normal keratinocytes, in which the SPCA1 mRNA was down-regulated with the small inhibitory RNA (siRNA) method. SiRNA inhibition significantly down-regulated the SPCA1 ... More
CASK deletion in intestinal epithelia causes mislocalization of LIN7C and the DLG1/Scrib polarity complex without affecting cell polarity.
AuthorsLozovatsky L, Abayasekara N, Piawah S, Walther Z,
JournalMol Biol Cell
PubMed ID19726564
'CASK is the mammalian ortholog of LIN2, a component of the LIN2/7/10 protein complex that targets epidermal growth factor receptor (EGFR) to basolateral membranes in Caenorhabditis elegans. A member of the MAGUK family of scaffolding proteins, CASK resides at basolateral membranes in polarized epithelia. Its interaction with LIN7 is evolutionarily ... More
Albumin endocytosis in proximal tubule cells is modulated by angiotensin II through an AT2 receptor-mediated protein kinase B activation.
AuthorsCaruso-Neves C, Kwon SH, Guggino WB,
JournalProc Natl Acad Sci U S A
PubMed ID16293694
'Albumin endocytosis in renal proximal tubule cells is a clathrin- and receptor-mediated mechanism that, in several pathophysiological conditions, is involved in initiating or promoting tubule-interstitial disease. Although much work has been done on this pathway, the regulation of albumin endocytosis in proximal tubule cells is not well understood. Here, we ... 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
Extracellular signal-regulated kinases 1/2 control claudin-2 expression in Madin-Darby canine kidney strain I and II cells.
AuthorsLipschutz JH, Li S, Arisco A, Balkovetz DF,
JournalJ Biol Chem
PubMed ID15569684
'The tight junction of the epithelial cell determines the characteristics of paracellular permeability across epithelium. Recent work points toward the claudin family of tight junction proteins as leading candidates for the molecular components that regulate paracellular permeability properties in epithelial tissues. Madin-Darby canine kidney (MDCK) strain I and II cells ... More
Distribution of tight junction proteins in adult human salivary glands.
AuthorsMaria OM, Kim JW, Gerstenhaber JA, Baum BJ, Tran SD
JournalJ Histochem Cytochem
PubMed ID18765838
'Tight junctions (TJs) are an essential structure of fluid-secreting cells, such as those in salivary glands. Three major families of integral membrane proteins have been identified as components of the TJ: claudins, occludin, and junctional adhesion molecules (JAMs), plus the cytosolic protein zonula occludens (ZO). We have been working to ... More
Abundant occurrence of basal radial glia in the subventricular zone of embryonic neocortex of a lissencephalic primate, the common marmoset Callithrix jacchus.
AuthorsKelava I, Reillo I, Murayama AY, Kalinka AT, Stenzel D, Tomancak P, Matsuzaki F, Lebrand C, Sasaki E, Schwamborn JC, Okano H, Huttner WB, Borrell V,
JournalCereb Cortex
PubMed ID22114084
'Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at ... More
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A.
AuthorsBell RD, Winkler EA, Singh I, Sagare AP, Deane R, Wu Z, Holtzman DM, Betsholtz C, Armulik A, Sallstrom J, Berk BC, Zlokovic BV,
JournalNature
PubMed ID22622580
Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and individuals with APOE4-associated disorders. ... More
Down-regulation of CD9 in human ovarian carcinoma cell might contribute to peritoneal dissemination: morphologic alteration and reduced expression of beta1 integrin subsets.
AuthorsFuruya M, Kato H, Nishimura N, Ishiwata I, Ikeda H, Ito R, Yoshiki T, Ishikura H,
JournalCancer Res
PubMed ID15805258
Peritoneal dissemination is one of the main causes of death in cancer patients. Pathophysiology of metastasis has been well investigated, but the mechanism of diffuse spread of tumor colonies in the peritoneal cavity is not fully understood. CD9 is a member of tetraspanin and its down-regulation is known to be ... More
Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations.
AuthorsBrooks TA, Hawkins BT, Huber JD, Egleton RD, Davis TP,
JournalAm J Physiol Heart Circ Physiol
PubMed ID15792985
The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). Recently it was shown that the BBB can be modulated by disease pathologies including inflammatory pain. This study ... More
The endothelial-cell-derived secreted factor Egfl7 regulates vascular tube formation.
AuthorsParker LH, Schmidt M, Jin SW, Gray AM, Beis D, Pham T, Frantz G, Palmieri S, Hillan K, Stainier DY, De Sauvage FJ, Ye W,
JournalNature
PubMed ID15085134
Vascular development is a complex but orderly process that is tightly regulated. A number of secreted factors produced by surrounding cells regulate endothelial cell (EC) differentiation, proliferation, migration and coalescence into cord-like structures. Vascular cords then undergo tubulogenesis to form vessels with a central lumen. But little is known about ... More
Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression.
AuthorsWitt KA, Mark KS, Hom S, Davis TP,
JournalAm J Physiol Heart Circ Physiol
PubMed ID12907427
Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. The effects of initial reoxygenation after a hypoxic insult (H/R) on functional and molecular properties of the BBB and TJs remain unclear. In situ brain perfusion and Western blot ... More
Cingulin and paracingulin show similar dynamic behaviour, but are recruited independently to junctions.
Cingulin (CGN) and paracingulin (CGNL1) are structurally related proteins that regulate Rho family GTPases by recruiting guanine nucleotide exchange factors to epithelial junctions. Although the subcellular localization of cingulin and paracingulin is likely to be essential for their role as adaptor proteins, nothing is known on their in vivo localization, ... More
Inhibition of the Raf/MEK/ERK pathway up-regulates expression of the coxsackievirus and adenovirus receptor in cancer cells.
AuthorsAnders M, Christian C, McMahon M, McCormick F, Korn WM,
JournalCancer Res
PubMed ID12727824
Recombinant adenoviruses are presently being tested clinically as a new strategy for the treatment of cancer. An important determining factor for the successful entry of such adenoviruses into target cells is expression of the coxsackievirus and adenovirus receptor (CAR) at the cell surface. Recent observations suggest that expression of this ... More
Functional organization of the bovine rumen epithelium.
AuthorsGraham C, Simmons NL,
JournalAm J Physiol Regul Integr Comp Physiol
PubMed ID15319221
The functional organization of the bovine rumen epithelium has been examined by electron and light microscopy combined with immunocytochemistry to define a transport model for this epithelium. Expression of connexin 43, an integral component of gap junctions, the tight-junction molecules claudin-1 and zonula occludens 1 (ZO-1), and the catalytic alpha-subunit ... More
An immunochemical marker for goldfish Mauthner cells.
AuthorsFlores CE, Ene S, Pereda AE,
JournalJ Neurosci Methods
PubMed ID18771692
The Mauthner (M-) cells are pair of large reticulospinal neurons that mediate tail-flip escape responses in fish. Exploring the co-localization of scaffold and gap junction proteins at mixed (electrical and chemical) synapses, we found that the use of a particular antibody against the scaffold protein Zonula Occludens-2 (ZO-2) resulted in ... More
Connexin43 associated with an N-cadherin-containing multiprotein complex is required for gap junction formation in NIH3T3 cells.
AuthorsWei CJ, Francis R, Xu X, Lo CW,
JournalJ Biol Chem
PubMed ID15741167
Previous studies have indicated an intimate linkage between gap junction and adherens junction formation. It was suggested this could reflect the close membrane-membrane apposition required for junction formation. In NIH3T3 cells, we observed the colocalization of connexin43 (Cx43alpha1) gap junction protein with N-cadherin, p120, and other N-cadherin-associated proteins at regions ... More
Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells.
AuthorsPrasad S, Mingrino R, Kaukinen K, Hayes KL, Powell RM, MacDonald TT, Collins JE,
JournalLab Invest
PubMed ID16007110
Claudin proteins comprise a recently described family of tight junction proteins that differentially regulate paracellular permeability. Since other tight junction proteins show alterations in distribution or expression in inflammatory bowel disease (IBD) we assessed expression of claudins (CL) 2, 3 and 4 in IBD. CL 2 was strongly expressed along ... 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
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
The carboxyl terminus of zona occludens-3 binds and recruits a Mammalian homologue of discs lost to tight junctions.
Authors Roh Michael H; Liu Chia-Jen; Laurinec Stephanie; Margolis Ben;
JournalJ Biol Chem
PubMed ID12021270
Mammalian homologues of the Drosophila polarity proteins Stardust, Discs Lost, and Crumbs have been identified as Pals1, Pals1-associated tight junction protein (PATJ), and human Crumbs homologue 1 (CRB1), respectively. We have previously demonstrated that PATJ, Pals1, and CRB1 can form a tripartite tight junction complex in epithelial cells and that ... More
The canonical NF-kappaB pathway governs mammary tumorigenesis in transgenic mice and tumor stem cell expansion.
The role of mammary epithelial cell (MEC) NF-?B in tumor progression in vivo is unknown, as murine NF-?B components and kinases either are required for murine survival or interfere with normal mammary gland development. As NF-?B inhibitors block both tumor-associated macrophages (TAM) and MEC NF-?B, the importance of MEC NF-?B ... 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
Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cells.
AuthorsPeerapen P, Thongboonkerd V
JournalLab Invest
PubMed ID20856225
Tight junction has a crucial role in regulating paracellular transports (as a barrier) and in separating apical from basolateral compartments to maintain cell polarity (as a fence). Tight junction can be disrupted by various stimuli, including oxidative stress, pathogens and proinflammatory cytokines. However, association of defective tight junction with kidney ... More