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Results for “Tight Junctions”

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At least 19 recordsLinked to original sources

PubMed1976

Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum.

Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum.

Animals↗

PubMed1975

Retinal capillary junctions: ultrastructural tight junction artefacts induced by sodium ions and membrane reduction in streptozotocin diabetes.

Retinal capillary junctions were analysed in normal and diabetic rats and in a human retina with the electron microscope. Diabetes mellitus was induced with streptozotocin. The retinae were fixed in Palade's osmium tetroxide containing sodium or calcium ions and block-stained in uranyl acetate. With Ca-fixation, no significant difference in interendothelial cleft width was detected between retinal layers or between normal and diabetic retinae. Diabetes caused a narrowing of the clefts in the Na-fixed tissue X +/- SE, n=375; Normal: 78.6 +/- 300 A; Diabetic: 57.7 +/- 2.42 A; p less than 0.001). A significant correlation was found between cleft width and the length of the tight junctions or zonulae occludentes (p less than 0.001). In the nerve fibre layer of the Na-diabetic retina, where cleft narrowing was greatest, there was an increase in length of the zonulae occludentes from 22.8 +/- 2.2% to 41.6 +/- 3.7% (p less than 0.001). Ca-fixation prevented these changes, indicating that at least some zonulae occludentes were interendothelial extraction artefacts. In the normal retina, endothelial cell membrane thickness was greater with Ca- than Na-fixation (p less than 0.001). Diabetes caused a decrease in membrane thickness of Ca-fixed tissue (p less than 0.001). The diabetic decrease in membrane thickness may explain the increased fragility and increased permeability of diabetic capillaries. Calcium binding by endothelial cell membranes is of primary importance in anticoagulation which is defective in diabetes.

Animals↗

PubMed1992

Diversity among tight junctions in rat kidney: glomerular slit diaphragms and endothelial junctions express only one isoform of the tight junction protein ZO-1.

ZO-1 is a 225-kDa peripheral membrane protein present in all tight junctions. It was recently shown to consist of two isoforms that differ in the presence of an internal 80-amino acid domain termed motif-alpha. To obtain information on their distribution and potential functional significance we have localized the two isoforms in rat kidney by using antibodies that recognize either both ZO-1 isoforms or the larger, motif-alpha-containing isoform. By immunofluorescence, staining with both antibodies was demonstrated at all tight junctions of tubular epithelial cells and the epithelial cells of Bowman's capsule. In contrast, the motif-alpha-containing isoform was absent from the slit diaphragms of the glomerular epithelium and the tight junctions of glomerular and peritubular capillary endothelial cells. This restricted isoform expression was confirmed by immunoblot analysis comparing proteins from purified glomeruli with those from kidney cortex or medulla. Thus, while both isoforms are expressed in typical epithelial tight junctions, only a single isoform, lacking motif-alpha, is expressed in the highly specialized slit diaphragms, where the intercellular spaces are normally open, and in endothelial junctions, which are readily opened by physiologic signals. The differential expression of ZO-1 isoforms in structurally and functionally distinct junctions in the kidney suggests that they may contribute to defining the variable functional properties, in particular the lability of these intercellular junctions.

Aging↗

PubMed1991

Maturation of the corneal endothelial tight junction.

Apical tight junctional formation of the rabbit corneal endothelium was examined by freeze-fracture analysis and measurement of paracellular permeability to 5(6)-carboxyfluorescein. Freeze-fracture analysis indicated that apical tight junction formation of the rabbit corneal endothelium is a dynamic process. At birth, there are few tight junctional strands present and a minimal barrier for paracellular diffusion. As the rabbit matures, a more complex network of anastomosing tight junctional strands begins to encircle the cell perimeter under the apical folds. However, even in the mature animal (3 months), there are discontinuities and free ends in the network, thus suggesting that the barrier is not complete even at this stage. Paracellular permeability measurements using 5(6)-carboxyfluorescein as a tracer corroborate these anatomic findings. Endothelial paracellular flux measurements steadily decrease as the rabbit matures from birth to young adult. This indicates that the tight junctional network is increasing in complexity and progressively limiting the flow of substances through the intercellular space.

Animals↗

PubMed1988

Cingulin, a new peripheral component of tight junctions.

The tight junction (Zonula occludens), a belt-like region of contact between cells of polarized epithelia, serves as a selective barrier to small molecules and as a total barrier to large molecules, and is involved in the separation between lumenal and basolateral compartments of the epithelium. In the electron microscope, tight junctions show focal regions of apparent fusion between the adjoining cell membranes, and freeze-fractured membranes display an elaborate network of branching and anastomosing strands. Very little is known about the molecular composition and architecture of tight junctions. The first specific zonula occludens-associated protein, designated ZO-1, has recently been identified in mammalian epithelial and endothelial cells. Here we describe the identification and purification of a new component of this junctional complex in avian brush-border cells, which we name cingulin. Cingulin is an acidic, heat-stable protein, with a highly elongated shape. Immunofluorescence and immunoelectron microscopy of brush-border cells with anti-cingulin antibodies show that cingulin is localized in the apical zone of the terminal web, at the endofacial surfaces of the zonula occludens.

Amino Acids↗

PubMed1992

Structure, function, and regulation of cellular tight junctions.

The tight junction (TJ) is a dynamic structure that is controlled, in part, by the activity of the cytoskeleton. It has become abundantly clear that, in the presence of Ca2+, assembly of the TJ is the result of cellular interactions that trigger a complex cascade of biochemical events that ultimately lead to the formation of an organized network of TJ elements, the composition of which remains unknown. The TJ functions both as a barrier between two fluid compartments and, to a lesser extent, as a fence between apical and basolateral membrane domains. To meet the many physiological and pathological challenges to which epithelia and endothelia are subjected, the TJ must be capable of a rapid and coordinated response, which depends on complex regulatory mechanisms. The precise characterization of the mechanisms involved in the assembly and regulation of the TJ is an area of current active investigation. However, until the biochemical composition of this structure has been defined and its gene identified, the TJ will continue to be an elusive yet tantalizing challenge to the cell biologist.

Animals↗

PubMed1988

Induction of gap junctions and brain endothelium-like tight junctions in cultured bovine endothelial cells: local control of cell specialization.

The final development of specializations by brain capillary endothelial cells, which characterize them as distinct from non-central nervous system (CNS) endothelium, is thought to be controlled by astrocyte-derived factors produced locally within the CNS. One specialization, the complex intercellular tight junction, which is unique to these cells and a major component of the blood-brain barrier, is controlled by an astrocyte-derived factor(s) and a "competent' extracellular matrix (Arthur et al., 1987). In order to test whether these factors can also trigger development of brain endothelium-like tight junctions in non-CNS microvessel endothelial cells, passaged bovine aorta and pulmonary artery endothelial cells were cultured in either 50% astrocyte-conditioned medium and 50% alpha-MEM, or in alpha-MEM alone (control). Only endothelial cells maintained in conditioned medium exhibited ultrastructural features indicative of synthesis and plasma membrane-insertion of junction components (Shivers et al., 1985). No assembled tight junctions were seen in these cells. Endothelial cells plated onto coverslips coated with ECM (Cedarlane Labs., Hornby, Ont.) and maintained in astrocyte-conditioned medium, displayed large, complex tight junctions and extraordinarily large gap junctions. Cells plated onto plastic or fibronectin-coated substrates possessed no tight or gap junctions. Results of this study show that CNS astrocytes produce a soluble factor(s) that promotes synthesis and insertion of tight junction components in non-CNS endothelial cells. Moreover, an intact, endothelial-derived extracellular matrix is required for assembly of tight junctions to complete development of this brain capillary-like specialization. This study confirms the notions that: a) the final fine-tuning of cell differentiation is under local control, and b) that endothelial cells in general do not express their final destination-specific differentiated features until those features are induced by local environment-produced conditions.

Animals↗

PubMed1991

Development of Sertoli cell junctional specializations and the distribution of the tight-junction-associated protein ZO-1 in the mouse testis.

Basally located tight junctions between Sertoli cells in the postpubertal testis are the largest and most complex junctional complexes known. They form at puberty and are thought to be the major structural component of the "blood-testis" barrier. We have now examined the development of these structures in the immature mouse testis in conjunction with immunolocalization of the tight-junction-associated protein ZO-1 (zonula occludens 1). In testes from 5-day-old mice, tight junctional complexes are absent and ZO-1 is distributed generally over the apicolateral, but not basal, Sertoli cell membrane. As cytoskeletal and reticular elements characteristic of the mature junction are recruited to the developing junctions, between 7 and 14 days, ZO-1 becomes progressively restricted to tight junctional regions. Immunogold labeling of ZO-1 on Sertoli cell plasma membrane preparations revealed specific localization to the cytoplasmic surface of tight junctional regions. In the mature animal, ZO-1 is similarly associated with tight junctional complexes in the basal aspects of the epithelium. In addition, it is also localized to Sertoli cell ectoplasmic specializations adjacent to early elongating, but not late, spermatids just prior to sperm release. Although these structures are not tight junctions, they do have a similar cytoskeletal arrangement, suggesting that ZO-1 interacts with the submembrane cytoskeleton. These results show that, in the immature mouse testis, ZO-1 is present on the Sertoli cell plasma membrane in the absence of recognizable tight junctions. In the presence of tight junctions, however, ZO-1 is found only at the sites of junctional specializations associated with tight junctions and with elongating spermatids.

Animals↗

PubMed1992

Structural domains of the tight junctional intramembrane fibrils.

Freeze-fracture reveals intramembrane fibrils lying along the intermembrane contacts that characterize tight junctions. Tight junctions from a variety of species are reexamined here by rapid freezing prior to freeze-fracture. The tight junction fibril is uprooted alternatively from either the cytoplasmic or the exoplasmic hemibilayer during freeze-cleavage, exposing two distinct but complementary views of its hybrid structure within the same replica. When the transmembrane fibril is uprooted from the exoplasmic hemibilayer it appears on the P-fracture face as a smooth-surfaced cylinder which is sometimes resolved into periodic globular structures. The lack of indication that the P-face cylinder has been pulled out through the opposite membrane half indicates that this domain of the fibril is, in large part, buried in the hydrophobic interior of the membrane. However, when the transmembrane fibril is uprooted from the cytosolic hemibilayer it appears on the E-fracture face as a row of irregular intramembrane particles. The irregular particles on the E-face aspect of the fibril are interpreted as corresponding to transmembrane protein segments that may very well make projections onto the cytosolic surface of the bilayer. En face views of the outermost junction strand between adjacent epithelial cells show periodic lines on the bilayer on each side of the junction which are interpreted as periodic transmembrane protein segments arising from the core structure of the tight junction fibril. If the backbone of the tight junction strand is an inverted cylindrical micelle, it must typically include proteins, which might anchor it to structures outside the membrane bilayer.

Animals↗

PubMed1989

The gastric mucosal barrier: tight junction structure in gastritis and ulcer biopsies.

Tight junctions of the human gastric mucosa were examined using quantitative freeze-fracture methods. Biopsies examined were from patients with gastric diseases including gastritis, ulcers, and pernicious anemia. No significant differences were seen in strand number or tight junction complex depth among the biopsies analyzed, however, anomalous tight junction structures were observed. Discontinuities in the tight junctions complex and hyperplastic tight junctions (extensions of the apical tight junction strands radiating over the lateral plasma membrane) were seen. These alterations were not associated exclusively with either the diagnosis of gastritis or ulcers. However, a higher frequency of tight junction breaks was seen in stomach biopsies diagnosed as gastritis while those diagnosed as ulcers displayed a higher occurrence of hyperplastic tight junctions.

Adult↗

PubMed1991

Hydrophobic ion transfer between membranes of adjacent hepatocytes: a possible probe of tight junction structure.

The topology of the tight junction is probed by introducing dipicrylamine (dpa-), a lipid-soluble anion, into the membranes of hepatocyte pairs in culture. Once partitioned into the membrane, dpa- ions are free to move in the hydrophobic core of the membrane, where their mobile charges greatly increase membrane capacitance. If tight junctions are lines of membrane fusion, dpa- will cross the tight junction without traversing a polar headgroup layer. Furthermore, the electric potential across the tight junction will be equal to the difference in membrane potentials of the two cells. dpa- can therefore be expected to move electrophoretically from cell membrane to cell membrane across the junction in response to an intercellular voltage difference. Experiments performed under double whole-cell clamp show that this transfer occurs as follows: First, dpa- causes an intercellular current unrelated to gap junctions to flow in response to an intercellular voltage difference. Second, this electrophoretic removal or addition of dpa- from a cell's membrane through the tight junction must reduce or increase its dpa- content and thus its capacitance. Experiments confirm this prediction: We detect rapid, symmetric, and reversible changes in membrane capacitance in response to changes in the membrane potential of the neighboring cell. Finally, we find that hepatocyte membranes contain a negatively charged endogenous molecule that contain a negatively charged endogenous molecule that can move from cell to cell like dpa- under the influence of an intercellular potential difference. We conclude that membrane fusion occurs at tight junctions and that this hydrophobic intercellular pathway can play a role in intercellular communication.

Animals↗

PubMed1989

Development of tight junctions de novo in the mouse early embryo: control of assembly of the tight junction-specific protein, ZO-1.

Tight junction development during trophectoderm biogenesis in the mouse preimplantation embryo has been examined using monoclonal antibodies recognizing the tight junction-specific peripheral membrane protein, ZO-1. In immunoblots, mouse embryo ZO-1 had a molecular mass (225 kD) equivalent to that in mouse liver, was barely detectable in four-cell embryos although later stages exhibited increasing levels. ZO-1 was first detected immunocytochemically at the compacting eight-cell stage, coincident with or just after the expression of basolateral cell adhesion and apical microvillous polarity. Initially, ZO-1 was present as a series of spots along the boundary between free and apposed cell surfaces in intact embryos or cell couplets, but subsequently staining became more linear with blastocyst trophectoderm cells being bordered by a continuous ZO-1 belt. Inhibition of cell adhesion at the 8-cell stage delayed ZO-1 appearance and randomized its surface distribution in a reversible manner. Microfilament disruption, but not microtubule depolymerization, produced major disturbances in ZO-1 distribution. ZO-1 assembly de novo appeared to be independent of proximate DNA and RNA synthesis but was inhibited substantially in the absence of protein synthesis during the eight-cell stage, a treatment that did not prevent intercellular adhesion and polarization. ZO-1 surface assembly, but not adhesion and polarization, was also perturbed when single eight-cells were combined with single four-cells. The results suggest that tight junction development in mouse embryos is a secondary event in epithelial biogenesis, being dependent upon cell adhesion and cytoskeletal activity for normal expression, and can be disrupted without disturbing the generation of a stably polarized phenotype.

Animals↗

PubMed1987

Intestinal absorptive cell tight junctions are linked to cytoskeleton.

Permeation of intercellular tight junctions in epithelia may be altered by maneuvers that affect the cytoskeleton. Conversely, agents that alter tight-junction permeability also often produce alterations in cytoskeletal structure. However, anatomic links between the tight junction and the cytoskeleton have not been clearly defined. We explore the anatomy of the perijunctional cytoskeleton by applying electron microscopy to cytoskeletal preparations of whole intestinal absorptive cells using detergent extraction techniques. Individual elements of the perijunctional cytoskeleton, including actin microfilaments as determined by S1 labeling, appear to associate with the tight junction by means of plaque-like densities that intimately associate with the lateral membrane at the site of the tight junction. Furthermore, such associations are not diffuse within the tight junction, but occur only at sites of fusions ("kisses") between lateral membranes that are thought to represent the specific intrajunctional sites at which the barriers to transjunctional permeation reside. These data provide evidence of intimate cytoskeletal-tight-junction associations, which may represent the anatomical basis for cytoskeletal control of tight-junction permeability.

Absorption↗

PubMed1988

Tight-junctional strands first appear in regions where three cells meet in differentiating olfactory epithelium: a freeze-fracture study.

Tight junctions of the olfactory epithelium of rat embryos were studied at the 14th day of gestation and during their subsequent development. Two different epithelial morphologies could be distinguished at the 14th gestational day. In one group of embryos the epithelial surface appeared undifferentiated, with tight-junctional strands found exclusively in regions where three cells met. The main orientation of these strands is in a direction parallel to the longitudinal orientation of the epithelial cells. These junctions resemble tight junctions that interconnect three cells, i.e. tricellular tight junctions, in that respect. However, unlike these the junctions mainly have single strands of particles, whereas tricellular junctions usually consist of paired strands of particles. Tight-junctional strands were completely absent in areas where two cells met. These areas, i.e. those of incipient bicellular tight junctions, had gap-junction-like aggregates of intramembranous particles. Another group of 14-day-old embryos displayed a differentiating olfactory epithelial surface with bicellular as well as tricellular tight-junctional strands. The latter ones were paired. Here too the tight-junctional belts displayed some gap-junction-like aggregates of particles, but there were considerably fewer of these than earlier. As one or the other tight-junctional appearance was always seen in a single freeze-fracture replica, it is reasonable to assume that the two tight-junctional appearances reflect a sequential pattern of differentiation peculiar to the whole surface of the olfactory epithelium, i.e. to surfaces of receptor cells as well as to surfaces of supporting cells. It would appear that, at the onset of olfactory epithelial differentiation, tight junctions first interconnect cells in regions where three cells meet and that tricellular strand formation precedes the formation of bicellular strands. When strands were present at the 14th day of embryonic development, their numbers were lower than those found later. However, strand packing, expressed as the density per micrometre of strands parallel to the epithelial surface, increased beginning at the 16th day of embryonic development.

Animals↗

PubMed1989

Filipin-induced deformations in plasma membranes of cultured bovine corneal endothelial cells with incomplete belts of tight junctions.

Complete belts of intact tight junctions are thought to act as barriers to the movement of cholesterol in the plane of the plasma membrane. As cholesterol can be revealed by filipin-induced membrane deformations on freeze-fracture images, we studied the distribution of these deformation in cultured bovine corneal endothelial cells with incomplete belts of tight junctions. While the extent of filipin-induced deformations differed between individual cells, there is a homogeneous distribution of filipin-induced deformations on both sides of the incomplete junctional belt of endothelial cells. Our results suggest that cultured endothelial cells do not polarize cholesterol, possibly because of the incomplete tight-junctional barrier.

Animals↗

PubMed1985

The structure of tight junctions in the ciliary epithelium.

The tight junctions of the ciliary epithelium act as a barrier preventing the passage of blood borne macromolecules into the posterior chamber. The use of the freeze-fracture technique has led to a good knowledge of their morphological pattern in various species. However, in order to attempt a correlation of the morphology of the tight junctions with their physiological properties, their intimate substructure must be considered. As in other glutaraldehyde-fixed epithelia, the tight junctions appear as networks (variable in their apico-basal thickness) of more or less discontinuous P-face ridges and as complementary E-face furrows in which some particles or short bars are found. The significance of the discontinuities of ridges has been analysed. The continuity of the junctional fibrils was evident as assessed both by quantitative measurements as well as morphological examination of complementary fracture faces. In addition, the absence of loss of junctional material showed that the integrity of the junction was preserved during the freeze-fracture process, even in conditions where an increase in "transfer" of junctional elements was experimentally induced. Most of all, a "pore system" due to visualizable gaps in the fibrils is not tenable for the ciliary epithelium. Furthermore, the analysis of transition steps at the level of membrane "fusion" showed that the tight junctions of the ciliary epithelium must now be considered as formed by two slightly offset fibrils, one per adjacent plasma membrane.

Animals↗

PubMed1985

Development of an apical plasma membrane domain and tight junctions during histogenesis of the mammalian pancreas.

The role of tight junctions (zonula occludens) in the formation of apical plasma membrane (PM) domains was investigated in the embryonic rat pancreas. In the present study, lectin-rhodamine (WGA-TRITC and RCAII-TRITC) and lectin-gold (WGA-Au and RCAII-Au) conjugates were used to monitor apical PM domain formation and freeze-fracture analysis was used to monitor tight junction formation in the pancreatic epithelium of embryonic, neonatal, and adult rats. Fluorescent and TEM analysis of WGA and RCAII binding indicated that an apical PM domain is formed as early as Day 13 of gestation in the pancreatic epithelium. While apical WGA binding remained into adult life, RCAII binding was lost by 1 day after birth. In contrast, tight junctions were not observed until Day 14 of gestation. At this time, tight junctions were found to be incomplete in formation and typically consisted of linear arrays of IMPs or discontinuous arrays of sealing strands (focal adherens). Continuous tight junctions were not completely formed until Day 15 of gestation. Continued development of tight junctions during gestation was characterized by (1) an increase in the number of sealing strands and (2) a more parallel arrangement of sealing strands within each junctional complex. By 8 weeks after birth, tight junctions were more loosely organized and contained fewer sealing strands as compared to that observed in the fetus. These results suggest that lateral diffusion of apical PM glycoconjugates may be restricted even in the absence of complete tight junctional complexes during development of the rat pancreas.

Animals↗

PubMed1977

Tracer and freeze fracture observations on developing tight junctions in fetal rat thyroid.

The development of tight junctions in fetal rat thyroid from the sixteenth to the twentieth days of gestation was examined with conventional ultrastructural methods and freeze-fracture preparations. These results were compared with those obtained using lanthanum hydroxide and horseradish peroxidase (HRP) tracers. Tight junctions appear to arise on the plasma membranes of fetal thyroid cells by the aggregation and fusion of linear particle chains which appear at several discrete sites on the plasma membrane of developing follicular cells. Tracer studies show that they are effective barriers to the passage of HRP from the outset, are freely penetrated by La3+ at the sixteenth and seventeenth days of gestation, but progressively lose permeability to La3+ from the seventeenth to twentieth days of gestation. However, freeze-fracture observations suggest that La3+ must penetrate into the follicular lumen through the tight junction elements, for the follicular lumen, when it appears, is always completely surrounded by a continuous though sometimes rudimentary meshwork of tight junction elements. The results suggest that the tight junction forms an effective barrier to the passage of large macromolecules, e.g. thyroglobulin, from very early stages in its development. The La3+ results suggest that decreased resistance of the intercellular pathway, possibly related to the development of transepithelial potentials, may occur during this period in development.

Animals↗