Focal adhesion kinase-Tyr407 and -Tyr397 exhibit antagonistic effects on blood-testis barrier dynamics in the rat.
AuthorsLie PP, Mruk DD, Mok KW, Su L, Lee WM, Cheng CY,
JournalProc Natl Acad Sci U S A
PubMed ID22797892
'Focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, displays phosphorylation-dependent localization in the seminiferous epithelium of adult rat testes. FAK is an integrated component of the blood-testis barrier (BTB) involved in regulating Sertoli cell adhesion via its effects on the occludin-zonula occludens-1 complex. Herein, we report that p-FAK-Tyr(407) and ... More
A biomimetic tissue from cultured normal human urothelial cells: analysis of physiological function.
AuthorsCross WR, Eardley I, Leese HJ, Southgate J,
JournalAm J Physiol Renal Physiol
PubMed ID15784840
'The urinary bladder and associated tract is lined by the urothelium. Once considered as just an impermeable epithelium, it is becoming evident that the urothelium not only functions as a volume-accommodating urinary barrier but has additional roles, including sensory signaling. Lack of access to normal human urothelium has hampered physiological ... More
rpS6 regulates blood-testis barrier dynamics through Akt-mediated effects on MMP-9.
AuthorsMok KW, Mruk DD, Cheng CY,
Journal
PubMed ID25217631
'Mammalian target of rapamycin complex 1 (mTORC1) is an emerging regulator of blood-tissue barriers that utilizes ribosomal protein S6 (rpS6) as the downstream signaling molecule. To explore the role of rpS6 in blood-testis barrier (BTB) function, a constitutively active quadruple rpS6 phosphomimetic mutant was constructed in mammalian expression vector and ... More
The tight junction protein ZO-2 localizes to the nucleus and interacts with the heterogeneous nuclear ribonucleoprotein scaffold attachment factor-B.
'Zonula occludens proteins (ZOPs), currently comprising ZO-1, ZO-2, and ZO-3, belong to the family of membrane-associated guanylate kinase homologue (MAGUK) proteins that are involved in the organization of epithelial and endothelial intercellular junctions. ZOPs bind to the cytoplasmic C termini of junctional transmembrane proteins linking them to the actin cytoskeleton. ... More
Truncation mutants of the tight junction protein ZO-1 disrupt corneal epithelial cell morphology.
AuthorsRyeom SW, Paul D, Goodenough DA,
JournalMol Biol Cell
PubMed ID10793144
'The tight junction is the most apical intercellular junction of epithelial cells and regulates transepithelial permeability through the paracellular pathway. To examine possible functions for the tight junction-associated protein ZO-1, C-terminally truncated mutants and a deletion mutant of ZO-1 were epitope tagged and stably expressed in corneal epithelial cell lines. ... More
Griffonia simplicifolia isolectin B4 identifies a specific subpopulation of angiogenic blood vessels following contusive spinal cord injury in the adult mouse.
AuthorsBenton RL, Maddie MA, Minnillo DR, Hagg T, Whittemore SR
JournalJ Comp Neurol
PubMed ID18092342
'After traumatic spinal cord injury (SCI), disruption and plasticity of the microvasculature within injured spinal tissue contribute to the pathological cascades associated with the evolution of both primary and secondary injury. Conversely, preserved vascular function most likely results in tissue sparing and subsequent functional recovery. It has been difficult to ... 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
Distribution of the tight junction proteins ZO-1, occludin, and claudin-4, -8, and -12 in bladder epithelium.
AuthorsAcharya P, Beckel J, Ruiz WG, Wang E, Rojas R, Birder L, Apodaca G,
JournalAm J Physiol Renal Physiol
PubMed ID15068973
'In mammals, the bladder stores urine without permitting the passage of urine contents into the bloodstream, a function, in part, of the uroepithelial-associated tight junction complex. The protein constituents that make up this high-resistance barrier in the bladder are currently unknown, although the claudins, a multigene family, are thought to ... More
CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS.
'Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in ... More
The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence.
AuthorsAlvarez JI, Dodelet-Devillers A, Kebir H, Ifergan I, Fabre PJ, Terouz S, Sabbagh M, Wosik K, Bourbonnière L, Bernard M, van Horssen J, de Vries HE, Charron F, Prat A
JournalScience
PubMed ID22144466
'The blood-brain barrier (BBB) is composed of tightly bound endothelial cells (ECs) and perivascular astrocytes that regulate central nervous system (CNS) homeostasis. We showed that astrocytes secrete Sonic hedgehog and that BBB ECs express Hedgehog (Hh) receptors, which together promote BBB formation and integrity during embryonic development and adulthood. Using ... More
Cyclooxygenase-2 deficiency leads to intestinal barrier dysfunction and increased mortality during polymicrobial sepsis.
AuthorsFredenburgh LE, Velandia MM, Ma J, Olszak T, Cernadas M, Englert JA, Chung SW, Liu X, Begay C, Padera RF, Blumberg RS, Walsh SR, Baron RM, Perrella MA
JournalJ Immunol
PubMed ID21967897
'Sepsis remains the leading cause of death in critically ill patients, despite modern advances in critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and the development of the multiple organ dysfunction syndrome during sepsis. Cyclooxygenase (COX)-2 is highly upregulated in the intestine during sepsis, and we hypothesized ... More
Invasive behavior of ulcerative colitis-associated carcinoma is related to reduced expression of CD44 extracellular domain: comparison with sporadic colon carcinoma.
AuthorsMikami T, Yoshida T, Numata Y, Kikuchi M, Araki K, Nakada N, Okayasu I
JournalDiagn Pathol
PubMed ID21473743
To elucidate relations of invasion of ulcerative colitis (UC)-associated carcinoma with its prognosis, the characteristics of invasive fronts were analyzed in comparison with sporadic colonic carcinomas. ... More
Leukocyte diapedesis in vivo induces transient loss of tight junction protein at the blood-retina barrier.
AuthorsXu H, Dawson R, Crane IJ, Liversidge J
JournalInvest Ophthalmol Vis Sci
PubMed ID15980240
Although much is now understood about the molecular structure of tight junctions (TJs), little is known about the regulation of their function during neural inflammatory disease processes in vivo. The mechanisms by which leukocytes transmigrate the blood-retina barrier (BRB) without affecting endothelial permeability are controversial. ... More
Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells.
AuthorsYu AS, McCarthy KM, Francis SA, McCormack JM, Lai J, Rogers RA, Lynch RD, Schneeberger EE,
JournalAm J Physiol Cell Physiol
PubMed ID15689410
The function of occludin (Occ) in the tight junction is undefined. To gain insight into its role in epithelial cell biology, occludin levels in Madin-Darby canine kidney II cells were suppressed by stably expressing short interfering RNA. Suppression of occludin was associated with a decrease in claudins-1 and -7 and ... More
Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells.
AuthorsYan HH, Mruk DD, Lee WM, Cheng CY,
JournalFASEB J
PubMed ID18192323
During spermatogenesis in the mammalian testis, preleptotene/leptotene spermatocytes differentiate from type B spermatogonia and traverse the blood-testis barrier (BTB) at stage VIII of the seminiferous epithelial cycle for further development. This timely movement of germ cells involves extensive junction restructuring at the BTB. Previous studies have shown that these events ... More
Scribble regulates an EMT polarity pathway through modulation of MAPK-ERK signaling to mediate junction formation.
AuthorsElsum IA, Martin C, Humbert PO,
Journal
PubMed ID23813956
The crucial role the Crumbs and Par polarity complexes play in tight junction integrity has long been established, however very few studies have investigated the role of the Scribble polarity module. Here, we use MCF10A cells, which fail to form tight junctions and express very little endogenous Crumbs3, to show ... More
The cytokine response of U937-derived macrophages infected through antibody-dependent enhancement of dengue virus disrupts cell apical-junction complexes and increases vascular permeability.
AuthorsPuerta-Guardo H, Raya-Sandino A, González-Mariscal L, Rosales VH, Ayala-Dávila J, Chávez-Mungía B, Martínez-Fong D, Medina F, Ludert JE, del Angel RM,
JournalJ Virol
PubMed ID23616663
Severe dengue (SD) is a life-threatening complication of dengue that includes vascular permeability syndrome (VPS) and respiratory distress. Secondary infections are considered a risk factor for developing SD, presumably through a mechanism called antibody-dependent enhancement (ADE). Despite extensive studies, the molecular bases of how ADE contributes to SD and VPS ... More
Allogeneic human mesenchymal stem cells restore epithelial protein permeability in cultured human alveolar type II cells by secretion of angiopoietin-1.
AuthorsFang X, Neyrinck AP, Matthay MA, Lee JW,
JournalJ Biol Chem
PubMed ID20554518
Acute lung injury is characterized by injury to the lung epithelium that leads to impaired resolution of pulmonary edema and also facilitates accumulation of protein-rich edema fluid and inflammatory cells in the distal airspaces of the lung. Recent in vivo and in vitro studies suggest that mesenchymal stem cells (MSC) ... More
Regulation of the blood-testis barrier by coxsackievirus and adenovirus receptor.
AuthorsSu L, Mruk DD, Cheng CY,
JournalAm J Physiol Cell Physiol
PubMed ID22875787
The blood-testis barrier (BTB) divides the seminiferous epithelium into the basal and the adluminal compartment. It restricts paracellular diffusion of molecules between Sertoli cells, confers cell polarity, and creates a unique microenvironment in the adluminal compartment for spermatid development. However, it undergoes restructuring during the epithelial cycle so that preleptotene ... More
Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.
AuthorsDíaz-Coránguez M, Segovia J, López-Ornelas A, Puerta-Guardo H, Ludert J, Chávez B, Meraz-Cruz N, González-Mariscal L,
JournalPLoS One
PubMed ID23637756
Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned ... More
Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission.
AuthorsBrimacombe CL, Grove J, Meredith LW, Hu K, Syder AJ, Flores MV, Timpe JM, Krieger SE, Baumert TF, Tellinghuisen TL, Wong-Staal F, Balfe P, McKeating JA
JournalJ Virol
PubMed ID20962076
Hepatitis C virus (HCV) can initiate infection by cell-free particle and cell-cell contact-dependent transmission. In this study we use a novel infectious coculture system to examine these alternative modes of infection. Cell-to-cell transmission is relatively resistant to anti-HCV glycoprotein monoclonal antibodies and polyclonal immunoglobulin isolated from infected individuals, providing an ... More
Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia.
AuthorsStevenson BR, Siliciano JD, Mooseker MS, Goodenough DA
JournalJ Cell Biol
PubMed ID3528172
A tight junction-enriched membrane fraction has been used as immunogen to generate a monoclonal antiserum specific for this intercellular junction. Hybridomas were screened for their ability to both react on an immunoblot and localize to the junctional complex region on frozen sections of unfixed mouse liver. A stable hybridoma line ... More
Drebrin, an actin-binding, cell-type characteristic protein: induction and localization in epithelial skin tumors and cultured keratinocytes.
AuthorsPeitsch WK, Hofmann I, Bulkescher J, Hergt M, Spring H, Bleyl U, Goerdt S, Franke WW
JournalJ Invest Dermatol
PubMed ID16185277
Isoform E2 of drebrin, an actin-binding protein originally identified in neuronal cells, has recently been identified in diverse non-neuronal cells, mostly in association with cell processes and intercellular junctions. Here, we report on the presence of drebrin in normal human skin, epithelial skin cancers, and cultured keratinocytes. Keratinocytes of normal ... More
Myosin IXa regulates epithelial differentiation and its deficiency results in hydrocephalus.
AuthorsAbouhamed M, Grobe K, San IV, Thelen S, Honnert U, Balda MS, Matter K, Bähler M
JournalMol Biol Cell
PubMed ID19828736
The ependymal multiciliated epithelium in the brain restricts the cerebrospinal fluid to the cerebral ventricles and regulates its flow. We report here that mice deficient for myosin IXa (Myo9a), an actin-dependent motor molecule with a Rho GTPase-activating (GAP) domain, develop severe hydrocephalus with stenosis and closure of the ventral caudal ... 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
Two strikingly different signaling pathways are induced by meningococcal type IV pili on endothelial and epithelial cells.
AuthorsLécuyer H, Nassif X, Coureuil M
JournalInfect Immun
PubMed ID22064711
Following adhesion on brain microvasculature, Neisseria meningitidis is able to cross the blood-brain barrier (BBB) by recruiting the polarity complex and the cell junction proteins, thus allowing the opening of the paracellular route. This feature is the consequence of the activation by the type IV pili of the ß2-adrenergic receptor/ß-arrestin ... More
Quaternary ammonium beta-cyclodextrin nanoparticles for enhancing doxorubicin permeability across the in vitro blood-brain barrier.
AuthorsGil ES, Li J, Xiao H, Lowe TL,
JournalBiomacromolecules
PubMed ID19216528
This study describes novel quaternary ammonium beta-cyclodextrin (QAbetaCD) nanoparticles as drug delivery carriers for doxorubicin (DOX), a hydrophobic anticancer drug, across the blood-brain barrier (BBB). QAbetaCD nanoparticles show 65-88 nm hydrodynamic radii with controllable cationic properties by adjusting the incorporated amount of quaternary ammonium group in their structure. ATR-FTIR studies ... More
Spermatogonial stem cells alone are not sufficient to re-initiate spermatogenesis in the rat testis following adjudin-induced infertility.
AuthorsMok KW, Mruk DD, Lee WM, Cheng CY
JournalInt J Androl
PubMed ID21696392
The blood-testis barrier (BTB) is a unique ultrastructure in the testis, which creates a specialized microenvironment in the seminiferous epithelium known as the apical (or adluminal) compartment for post-meiotic germ-cell development and for maintenance of an immunological barrier. In this study, we have demonstrated unequivocally that a functional and intact ... More