Distribution of the tight junction-associated protein ZO-1 in circumventricular organs of the CNS

Petrov, Tatjana; Howarth, Andrew G; Krukoff, Teresa L.; Stevenson, Bruce R.

doi:10.1016/0169-328x(94)90254-2

Cited by 82 publications

(63 citation statements)

References 38 publications

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“…Ependymal cells are interconnected via numerous gap junctions, and some ependyma also express TJ associated proteins such as occludins and ZO-1 (Lippoldt et al, 2000;Petrov et al, 1994). Future studies using GlialCAM deficient mice might help to elucidate the potential role of GlialCAM in the CSF/CNS barrier.…”

Section: Discussionmentioning

confidence: 97%

GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

Favre-Kontula

Rolland

Bernasconi

et al. 2008

Glia

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Using structure based genome mining targeting vascular endothelial and platelet derived growth factor immunoglobulin (Ig) like folds, we have identified a sequence corresponding to a single transmembrane protein with two Ig domains, which we cloned from a human brain cDNA library. The cDNA is identical to hepatocyte cell adhesion molecule (hepaCAM), which was originally described as a tumor suppressor gene in liver. Here, we show that the protein is predominantly expressed in the mouse and human nervous system. In liver, the expression is very low in humans, and is not detected in mice. To identify the central nervous system (CNS) regions and cell types expressing the protein, we performed a LacZ reporter gene assay on heterozygous mice in which one copy of the gene encoding the novel protein had been replaced with beta-galactosidase. beta-galactosidase expression was prominent in white matter tracts of the CNS. Furthermore, expression was detected in ependymal cells of the brain ventricular zones and the central canal of the spinal cord. Double labeling experiments showed expression mainly in CNPase positive oligodendrocytes (OL). Since the protein is predominantly expressed in the CNS glial cells, we named the molecule glial cell adhesion molecule (GlialCAM). A potential role for GlialCAM in myelination was supported by its up-regulation during postnatal mouse brain development, where it was concomitantly expressed with myelin basic protein (MBP). In addition, in vitro, GlialCAM was observed in various developmental stages of OL and in astrocytes in processes and at cell contact sites. In A2B5 positive OL, GlialCAM colocalizes with GAP43 in OL growth cone like structures. Overall, the data presented here indicate a potential function for GlialCAM in glial cell biology.

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Section: Discussionmentioning

confidence: 97%

GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

Favre-Kontula

Rolland

Bernasconi

et al. 2008

Glia

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“…It was shown to be a cytoplasmic component of adherens junctions (Itoh et al, 1991(Itoh et al, , 1993Howarth et al, 1992), as well as gap junctions (Thomas et al, 2002). Studies of ZO-1 in the CNS have indicated restricted expression patterns, with localization to vascular, circumventricular and developing neuroepithelial cell types (Dermietzel and Krause, 1991;Howarth et al, 1992;Smith and Shine, 1992;Petrov et al, 1994;Aaku-Saraste et al, 1996;Saitou et al, 1997;Wolburg and Lippoldt, 2002;Vorbrodt and Dobrogowska, 2003), and a few types of neurons in the olfactory system and hippocampus (Miragall et al, 1994;Inagaki et al, 2003). However, we have found a much wider distribution of ZO-1 in the CNS, including its localization at inter-neuronal gap junctions composed of Cx36 (Li et al, 2004).…”

Section: Cx47 Association With Zo-1mentioning

confidence: 99%

Connexin47, connexin29 and connexin32 co-expression in oligodendrocytes and cx47 association with zonula occludens-1 (zo-1) in mouse brain

et al. 2004

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Gap junctions between glial cells in mammalian CNS are known to contain several connexins (Cx), including Cx26, Cx30 and Cx43 at astrocyte-to-astrocyte junctions, and Cx29 and Cx32 on the oligodendrocyte side of astrocyte-to-oligodendrocyte junctions. Recent reports indicating that oligodendrocytes also express Cx47 prompted the present studies of Cx47 localization and relationships to other glial connexins in mouse CNS. In view of the increasing number of connexins reported to interact directly with the scaffolding protein zonula occludens-1 (ZO-1), we investigated ZO-1 expression and Cx47/ZO-1 interaction capabilities in brain, spinal cord and Cx47-transfected HeLa cells. From counts of over 9000 oligodendrocytes labeled by immunofluorescence in various brain regions, virtually all of these cells were found to express Cx29, Cx32 and Cx47. Oligodendrocyte somata displayed robust Cx47-immunopositive puncta that were co-localized with punctate labeling for Cx32 and Cx43. By freeze-fracture replica immunogold labeling, Cx47 was abundant on the oligodendrocyte-side of oligodendrocyte/astrocyte gap junctions. By immunofluorescence, labeling for Cx47 along myelinated fibers was sparse in most brain regions, whereas Cx29 and Cx32 were previously found to be concentrated along these fibers. By immunogold labeling, Cx47 was found in numerous small gap junctions linking myelin to astrocytes, but not within deeper layers of myelin. Brain subcellular fractionation revealed a lack of Cx47 enrichment in myelin fractions, which nevertheless contained an enrichment of Cx32 and Cx29. Oligodendrocytes were immunopositive for ZO-1, and displayed almost total Cx47/ZO-1 colocalization. ZO-1 was found to co-immunoprecipitate with Cx47, and pull-down assays indicated binding of Cx47 to the second PDZ domain of ZO-1.Our results indicate widespread expression of Cx47 by oligodendrocytes, but with a distribution pattern in relative levels inverse to the abundance of Cx29 in myelin and paucity of Cx29 in oligodendrocyte somata. Further, our findings suggest a scaffolding and/or regulatory role of ZO-1 at the oligodendrocyte side of astrocyte-to-oligodendrocyte gap junctions. Keywords connexin47; connexin32; connexin43; gap junctions; PDZ domains; glia Gap junctions are localized at specialized cell-to-cell contacts of plasma membranes in which connexin (Cx) proteins form bidirectional intercellular channels that allow passage of ions and *Corresponding author. Tel: +1-204-789-3767; fax: +1-204-789-3934. E-mail address: nagyji@ms.umanitoba.ca (J. I. Nagy).. 1 Present address: Department of Pathology, Weifang Medical College, PR China. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2007 March 8. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscriptsmall molecules between cells (Goodenough et al., 1996;Kumar and Gilula, 1996;Willecke et al., 2002). In the CNS, astrocytes are extensively coupled by gap junctions (astrocyte-toastrocyte gap junctions [A/A junctions]) that, base...

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“…Ependyma also have transport systems and distinct enzymes able to remove endogenous and exogenous toxins from the nervous system (Abramovitz et al, 1988;Cammer et al, 1989;Carder et al, 1990). In addition, ependyma express ZO1, occludin, cadherin, α-catenin and β-catenin which are some of junctional complex proteins known to provide the anatomical basis of the CNS barriers (Lippoldt et al, 2000a;Petrov et al, 1994). These chemical and mechanical elements provide ependyma the properties to act as a filtration barrier that protects the brain from potentially harmful substances present in the CSF (Kuchler et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Differential changes in junctional complex proteins suggest the ependymal lining as the main source of leukocyte infiltration into ventricles in murine neurocysticercosis

Alvarez

Teale

2007

Journal of Neuroimmunology

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The blood brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCB) limit the influx of immune mediators and bloodstream compounds into the central nervous system (CNS). Upon injury or infection, the integrity of these barriers is compromised and leukocyte infiltration occurs. The BCB is located in the choroid plexuses (CPs) found within ventricles of the brain, and it is considered one of the main routes of cellular infiltration into the CNS into healthy individuals. Our group recently showed that in a murine model of neurocysticercosis (NCC), there is a moderate increase in infiltration of leukocytes into ventricles, but the BCB is hardly compromised. To elucidate the role played by CPs and surrounding ependyma in leukocyte infiltration at ventricular sites, we analyzed changes in the expression of junctional complex proteins in animals intracranially infected with Mesocestoides corti. The results indicate that infection does not change the expression pattern of junctional complex proteins in CPs, but structural alterations and disappearance of these proteins were evident in ependyma adjacent to the internal leptomeninges. The kinetics and magnitude of these changes directly correlated with the extent of leukocyte infiltration through ependyma and with the expression and activity of MMPs. The results of this study indicate that the anatomical elements of the BCB are minimally disrupted during the course of murine NCC. Thus, most of the leukocytes infiltrating ventricles appear to extravasate through pial vessels located in the internal leptomeninges juxtaposed to the ependyma layer and then traverse the ependyma cells. In addition, MMP activity seems to be involved in this process. These results provide evidence for a previously undescribed entry route for leukocytes into the CNS.

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Distribution of the tight junction-associated protein ZO-1 in circumventricular organs of the CNS

Cited by 82 publications

References 38 publications

GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

GlialCAM, an immunoglobulin‐like cell adhesion molecule is expressed in glial cells of the central nervous system

Connexin47, connexin29 and connexin32 co-expression in oligodendrocytes and cx47 association with zonula occludens-1 (zo-1) in mouse brain

Differential changes in junctional complex proteins suggest the ependymal lining as the main source of leukocyte infiltration into ventricles in murine neurocysticercosis

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