THE TIGHT JUNCTION: Morphology to Molecules

Stevenson, Bruce R.; Keon, Brigitte H.

doi:10.1146/annurev.cellbio.14.1.89

Cited by 231 publications

(164 citation statements)

References 121 publications

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“…The AJ consists of integral membrane proteins (cadherins) and cytoplasmic proteins (␣-, ␤-, and ␥-catenins) that link cadherins to the actin cytoskeleton (Yap et al, 1997;Steinberg and McNutt, 1999). The TJ is also composed of both integral (occludin, claudin) and peripheral (ZO-1, -2, and -3, cingulin) membrane proteins linked to the actin cytoskeleton (Mitic and Anderson, 1998;Stevenson and Keon, 1998;Fanning et al, 1999;Tsukita and Furuse, 1999). TJs function as seals to restrict the passage of proteins through the intercellular spaces, as fences to prevent the mixing of apical and basolateral plasmalemmal domains, and as channels to regulate the passage of ions and water through the intercellular spaces (Mitic and Anderson, 1998;Stevenson and Keon, 1998;Fanning et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…The TJ is also composed of both integral (occludin, claudin) and peripheral (ZO-1, -2, and -3, cingulin) membrane proteins linked to the actin cytoskeleton (Mitic and Anderson, 1998;Stevenson and Keon, 1998;Fanning et al, 1999;Tsukita and Furuse, 1999). TJs function as seals to restrict the passage of proteins through the intercellular spaces, as fences to prevent the mixing of apical and basolateral plasmalemmal domains, and as channels to regulate the passage of ions and water through the intercellular spaces (Mitic and Anderson, 1998;Stevenson and Keon, 1998;Fanning et al, 1999). Many lines of evidence suggest that paracellular permeability through TJ is influenced by the state of perijunctional actin (Madara et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

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Expression of Podocalyxin Inhibits Cell–Cell Adhesion and Modifies Junctional Properties in Madin-Darby Canine Kidney Cells

Takeda¹,

Go²,

Orlando

et al. 2000

MBoC

184

181

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Podocalyxin is a major membrane protein of the glomerular epithelium and is thought to be involved in maintenance of the architecture of the foot processes and filtration slits characteristic of this unique epithelium by virtue of its high negative charge. However, until now there has been no direct evidence for podocalyxin's function. Podocalyxin is a type 1 transmembrane sialoprotein with an N-terminal mucin-like domain. To assess its function, we cloned rat podocalyxin and examined the effects of its expression on the cell adhesion properties of stably transfected Chinese hamster ovary (CHO)-K1 and Madin-Darby canine kidney (MDCK) cells and inducible ecdysone receptor-expressing (EcR)-CHO cells. In a cell aggregation assay, CHO-K1 cells expressing high levels of podocalyxin showed complete inhibition of cell aggregation, and MDCK transfectants showed greatly reduced aggregation (ϳ60 -80%) compared with parental cells. In EcR-CHO cells, the expression level of podocalyxin induced by increasing levels of ecdysone analogue correlated closely with the antiadhesion effect. The inhibitory effect of podocalyxin was reversed by treatment of the cells with Arthrobacter ureafaciens sialidase, indicating that sialic acid is required for inhibition of cell adhesion. Overexpression of podocalyxin also affected transepithelial resistance and the distribution of junctional proteins in MDCK cells by an unknown mechanism that may involve interaction with the actin cytoskeleton. These results provide direct evidence that podocalyxin functions as an antiadhesin that maintains an open filtration pathway between neighboring foot processes in the glomerular epithelium by charge repulsion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expression of Podocalyxin Inhibits Cell–Cell Adhesion and Modifies Junctional Properties in Madin-Darby Canine Kidney Cells

Takeda¹,

Go²,

Orlando

et al. 2000

MBoC

184

181

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“…Tight junctions form a barrier that regulates the paracellular transit of water, solutes, and immune cells across an epithelium (10), and are essential for establishing cell polarity by separating the apical and basolateral domains of polarized epithelial cells (11). ZO-1, the first tight junction protein identified (12,13), is an intracellular peripheral membrane scaffolding protein important for tight junction structure and assembly.…”

Section: G Roup B Coxsackieviruses and A Number Of Adenovirus Serotypesmentioning

confidence: 99%

The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction

Cohen

Shieh

Pickles

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

610

537

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The coxsackievirus and adenovirus receptor (CAR) mediates viral attachment and infection, but its physiologic functions have not been described. In nonpolarized cells, CAR localized to homotypic intercellular contacts, mediated homotypic cell aggregation, and recruited the tight junction protein ZO-1 to sites of cell-cell contact. In polarized epithelial cells, CAR and ZO-1 colocalized to tight junctions and could be coprecipitated from cell lysates. CAR expression led to reduced passage of macromolecules and ions across cell monolayers, and soluble CAR inhibited the formation of functional tight junctions. Virus entry into polarized epithelium required disruption of tight junctions. These results indicate that CAR is a component of the tight junction and of the functional barrier to paracellular solute movement. Sequestration of CAR in tight junctions may limit virus infection across epithelial surfaces.G roup B coxsackieviruses and a number of adenovirus serotypes initiate infection by binding to the coxsackievirus and adenovirus receptor (CAR) (1-3). CAR is a 46-kDa integral membrane protein with a typical transmembrane region, a long cytoplasmic domain, and an extracellular region composed of two Ig-like domains (1, 2). Both adenovirus (4) and coxsackievirus (5) interact with the N-terminal domain. Homologs of human CAR have been characterized in mice (2, 6), rats, pigs, dogs (7), and zebrafish (8). The murine and human proteins are very similar (91% amino acid identity within the extracellular domain, 77% within the transmembrane domain, and 95% identity within the cytoplasmic domain). Variant isoforms of CAR, which differ only at the C terminus and which most likely result from alternative splicing, have been identified in mice (6), humans, and rats (7). Despite evidence of its evolutionary conservation in mammals and nonmammalian vertebrates, the function of CAR is not known.Tight junctions are continuous circumferential intercellular contacts at the apical poles of lateral cell membranes, appearing in electron micrographs as a series of discrete contacts between the plasma membranes of adjacent cells (9). Tight junctions form a barrier that regulates the paracellular transit of water, solutes, and immune cells across an epithelium (10), and are essential for establishing cell polarity by separating the apical and basolateral domains of polarized epithelial cells (11). ZO-1, the first tight junction protein identified (12, 13), is an intracellular peripheral membrane scaffolding protein important for tight junction structure and assembly. In the present study, we found that in polarized epithelial cells CAR is expressed at the tight junction, where it associates with ZO-1 and functions in the barrier to the movement of macromolecules and ions. Materials and MethodsCell Culture. T-84, CALU-3, and 16HBE14o-cells were grown in 10% CO 2 in a 1:1 mixture of DMEM and Ham's F-12 medium with 10% FCS. To establish polarized monolayers, 5 ϫ 10 5 cells per well were plated on 12-mm diameter polyester filters with a ...

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“…One line of supporting evidence comes from the normal cellular expression pattern: MUC1 is expressed at the apical surface of ductal epithelia, in contrast to adhesion molecules found on the basal and lateral surfaces that are in tight contact with surrounding cells or stromal elements. 24 Specific localization of MUC1 to the apical surface of the ductal lumen may contribute to establishment and maintenance of the zone of cell surface that is exposed to the lumen and is not in contact with adjoining cells. Loss of cellular polarity, which accompanies transformation of cells, results in loss of apical expression of MUC1.…”

mentioning

confidence: 99%

Overexpression of MUC1 reconfigures the binding properties of tumor cells

et al. 2001

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Although it is known that adhesion and antiadhesion are essential to the metastatic spread of tumor cells, little is known about the molecules that regulate these processes. Key words: selectin; metastasis; ICAM-1; pancreatic cancer; colon cancerHuman MUC1 1-4 is a large, type I transmembrane protein normally expressed on the apical surface of ductal epithelia. 5 MUC1 is synthesized as a single polypeptide chain but exists on the cell surface as a heterodimer. Proteolytic cleavage of the full-length protein results in 2 associated fragments: a large extracellular polypeptide containing the tandem repeat domain that can be released from the cell surface and a polypeptide consisting of the short extracellular domain, the transmembrane domain and the cytoplasmic tail that exists as an integral membrane protein. 6 -8 The tandem repeat domain of MUC1 is rich in serines and threonines and is heavily glycosylated with complex O-linked oligosaccharides. Fully processed forms of MUC1 produced by different secretory epithelia (e.g., pancreas, mammary gland, kidney, lung) are distinct in part because of differential glycosylation. 6,9 -12 Levels of expression and types of posttranslational modifications of MUC1 by transformed epithelial cells often differ from forms produced by corresponding normal epithelia. [13][14][15][16][17][18][19] The appearance of novel oligosaccharide structures on MUC1 expressed by tumors (compared with normal epithelia) or differential glycosylation at different positions on the MUC1 core protein may confer new properties of adhesion that contribute to the ability of tumor cells to metastasize. For example, certain glycoforms of MUC1 have been shown to associate with intracellular adhesion molecule 1 (ICAM-1), 20 and it is predicted that certain oligosaccharide structures present on MUC1, such as sialyl Lewis A (sLe a ) or sialyl Lewis X (sLe x ) 15,21 interact with different lectin-like molecules 22 that influence general properties of cell adhesion.There is also evidence for a seemingly opposing hypothesis: that MUC1 can have "antiadhesive" properties at the cell surface. Some allelic forms of MUC1 extend 200 -500 nm above the plasma membrane, 23 which implies that the extracellular domain of MUC1 can extend more than 150 -450 nm above the estimated length of other cell surface adhesion molecules. These physical properties, together with observed differences in morphologic properties of cells overexpressing MUC1, have led to the proposal of an antiadhesion function for MUC1. One line of supporting evidence comes from the normal cellular expression pattern: MUC1 is expressed at the apical surface of ductal epithelia, in contrast to adhesion molecules found on the basal and lateral surfaces that are in tight contact with surrounding cells or stromal elements. 24 Specific localization of MUC1 to the apical surface of the ductal lumen may contribute to establishment and maintenance of the zone of cell surface that is exposed to the lumen and is not in contact with adjoining cells. Loss of cellu...

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THE TIGHT JUNCTION: Morphology to Molecules

Cited by 231 publications

References 121 publications

Expression of Podocalyxin Inhibits Cell–Cell Adhesion and Modifies Junctional Properties in Madin-Darby Canine Kidney Cells

Expression of Podocalyxin Inhibits Cell–Cell Adhesion and Modifies Junctional Properties in Madin-Darby Canine Kidney Cells

The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction

Overexpression of MUC1 reconfigures the binding properties of tumor cells

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