What do intercellular junctions do




















Three different types of intercellular junctions can be distinguished according to their function:. This type of junction is also called zonula occludens and is the most apical structure in the epithelial cell. Zonula occludens describes, that there is a formed band of tight junctions which encircles every cell. The main tight junction forms a seal between the two membranes.

This seal consists of the transmembrane proteins caudin and occludin and provide transcellular and paracellular transport of molecules, but prevent passive flow between cells. In addition the band of tight junctions separates the epithelial cell into apical and basolateral membrane domains.

As well as the tight junctions the adherent junctions build an encircling structure just below, called zonula adherens. One main function of the zonulae is strengthening and stabilizing the circular occluding bands. Another important function is the linking cytoskeletons of adjacent cells. Cadherins binds catenin via actin binding proteins to actin filaments to their cytoplasmic ends and builds hence the terminal web. This is in concordance with the known function of TJP1 as an intracellular scaffolding molecule.

Expression of occludin was diffuse, and the intensity was highest in the parabasal epithelium Fig. Because adhesion molecule expression patterns were identical in the ectocervical and vaginal epithelia, only images for the ectocervix are shown.

Junctional molecules of the ectocervix and vagina visualized by immunocytochemistry Cy3-labeled antibodies appear red; DAPI-stained nuclei appear blue.

All junctional molecules studied were detected in both ectocervical and vaginal tissues, displaying a spiderweb-like pattern throughout the epithelium. Ectocervical staining patterns are shown here.

Cy3-labeled IgG was excluded by the tight junctions of the endocervical single-cell columnar epithelium Fig. In contrast, fluorescent Cy3-labeled IgG penetrated the superficial layers of the ectocervical mucosal epithelium Fig. As noted above, these apical layers are composed of cornified epithelial cells that do not appear to have exclusionary epithelial adhesion junctions.

Below these cells, approximately three or four cellular layers from the lumen, epithelial junctions restricted the diffusion of labeled IgG between epithelial cells. Cervical permeability to Cy3-labeled red IgG. The endocervical epithelium provided a robust barrier to penetration of Cy3-tagged IgG, whereas the most apical layers of the ectocervix were permeable. A Endocervical tissue incubated with Cy3-labeled IgG. No diffusion is seen into the epithelium past the tight junctional complex left arrow.

The arrow on the right indicates a compromised epithelial cell. B Cy3-labeled IgG penetrated the apical cellular layers of ectocervical epithelium. Cervicovaginal epithelial barrier integrity is maintained by intercellular junctions that prevent the invasion of microbes, with the exception of certain pathogenic organisms that have developed strategies to breech the epithelial barrier.

Many other factors further fortify this barrier. Mucus produced by cervical and vaginal epithelial cells forms a glycocalyx on the epithelial surface that retains immunological mediators, including immunoglobulins and antimicrobial peptides [ 20 — 23 ]. Furthermore, a variety of leukocytes migrate into and through the epithelium to conduct immunosurveillance [ 23 , 24 ]. The purpose of the present study was to characterize cervical and vaginal epithelial junctions to better understand their role in STI pathogenesis and immune defense of the lower female genital tract.

Our electron-microscopy studies indicate that classical tight junctions comprise the principal intracellular junctions between epithelial cells in the endocervix, in accordance with the current knowledge of the structure of simple columnar epithelia [ 25 ].

These tight junctions formed a barrier that was impermeable to Cy3-labeled IgG. In contrast, the uppermost layers of the stratified squamous ectocervical epithelium were devoid of organized intracellular junctions, and the apical layers were permeable to Cy3-labeled IgG.

Exclusionary junctions were observed directly beneath this layer, and IgG did not penetrate beyond this point. The present study also surveyed the expression of discrete junctional molecules representing the different types of intracellular junctions in both the columnar epithelium of the endocervix and the stratified squamous epithelium of the ectocervix and vagina.

The results from this investigation indicate that F11R, E-cadherin, occludin, claudin-1, and TJP1 are abundant junctional molecules in the human endocervix. JAM3, a desmosomal junctional molecule, was not detected in the endocervix. Claudin-1 expression was found in distinct foci, whereas the other junctional molecules were expressed uniformly at sites of cellular contact throughout the epithelium. Previous studies of cervical cancer biomarkers have described select junctional proteins in human cervical tissue.

E-cadherin was previously described in the endocervical mucosa [ 26 ], and images published by Lee et al. All of the intracellular junctional proteins surveyed in the present study, including JAM3, were detected in ectocervical and vaginal stratified squamous epithelia. The ectocervix is structurally a part of the vaginal wall and shares a continuous, morphologically identical mucosal layer with vaginal tissue [ 19 ].

Each of these molecules displayed a spiderweb-like distribution in the basal and suprabasal layers consistent with their functions as mediators of cell-cell adhesion. Little or no staining was observed in the most apical layers, where the epithelial cells gradually lose cell-cell contacts and are eventually sloughed into the lumen.

Claudin-1, occludin, TJP1, and E-cadherin expression has been previously described in the human ectocervix [ 14 , 27 ]. Claudin-4 and claudin-7 have been also detected in ectocervical and vaginal epithelial cells [ 14 ]. JAM3 expression has not been well studied in stratified squamous epithelia and has not been detected previously in the female mucosal epithelium, but it has been observed in the endothelium and retinal epithelium [ 18 , 28 ].

The structure and distribution of adhesion molecules in the endocervical columnar epithelium and cervicovaginal squamous epithelium, as revealed by the present study, are diagrammed in Figure 6.

Localization of selected interepithelial adhesion molecules in the female lower genital tract. A The endocervical epithelium contains classic tripartite junctions. The tight junctions are located near the apical surface; they seal the epithelium and maintain cellular polarity. Adherens junctions are located directly below the tight junctions and are primarily responsible for cell-cell adhesion.

E-cadherin is the common transcellular component of all epithelial adherens junctions and is anchored to the actin cytoskeleton by vinculin and alpha and beta catenins. Desmosomes are the most basal adhesion structure and endow the tissue with mechanical resistance and strength. The major extracellular components of the desmosome are desmoglein and desmocollin, which connect to intermediate filaments of adjacent cells through an intracellular scaffolding network.

B The most robust junctions in the stratified squamous epithelium of the ectocervix and vagina lie in the parabasal epithelium, just above the basal layer in contact with the basement membrane. Adherens junctions are particularly abundant. The integrity of the junctions progressively lessens as epithelial cells are pushed toward the apical surface, where they become cornified, lose all cellular contacts, and are sloughed into the lumen.

Some pathogens are known to affect the integrity of epithelial junctions to facilitate transmission across the mucosal surface.

In the context of the female reproductive tract, Nazli et al. This correlated with increased production of the proinflammatory cytokine tumor necrosis factor-alpha and disruption of the tight junctional molecules TJP1, occludin, and claudin-1, -2, and -4 [ 16 ]. F11R is a known ligand of lymphocyte-associated antigen 1 expressed on T cells, macrophages, and neutrophils; it may provide a foothold for migratory leukocytes [ 17 , 29 ].

Similarly, E-cadherin is a receptor for the lymphocyte adhesion molecule alphaEbeta7 integrin on T cells [ 30 ]. In contrast to tight and adherens junctions, little evidence indicates that desmosomal structure is altered by pathogen invasion or inflammation [ 31 ]. However, the desmosomal molecule JAM3 is a ligand for the macrophage-1 receptor on macrophages and neutrophils, and JAM3 regulates the influx of leukocytes, particularly neutrophils, in response to inflammatory stimuli [ 18 ].

For a leukocyte to migrate between epithelial cells, the epithelial junctional bonds must be disrupted. Permeability to infiltrating leukocytes is largely regulated by secreted proinflammatory cytokines and chemokines [ 32 ].

A definitive understanding about the composition of cervical and vaginal epithelial junctions also provides an important foundation for future studies on pathogen transmission. For infections such as HIV, preventing epithelial barrier breach by cell-free or cell-associated virus is of the utmost importance [ 33 ].

Results from the present study indicate that the uppermost layers of the stratified squamous epithelium covering the vagina and ectocervix may not comprise a physical barrier against STIs but, rather, a potential zone for interactions with immunological mediators that may be retained at this site.

Mapping the normal expression of key molecular regulators of barrier resistance is an important first step in elucidating how microbes take advantage of these mechanisms to infect a host.

Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance Atlanta, GA: U. Department of Health and Human Services; World Health Organization. Tight junctions and compositionally related junctional structures in mammalian stratified epithelia and cell cultures derived therefrom. Eur J Cell Biol ; 81 : — Google Scholar. Epithelial barriers in homeostasis and disease. Annu Rev Pathol ; 5 : — Meng W , Takeichi M. Adherens junction: molecular architecture and regulation.

Cold Spring Harb Perspect Biol ; 1 : 1 — Desmosomes: new perspectives on a classic. J Invest Dermatol ; : — Gorodeski GI. Estrogen decrease in tight junctional resistance involves matrix-metalloproteinasemediated remodeling of occludin. Endocrinology ; : — Molecular physiology and pathophysiology of tight junctions. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Tight junctions and human diseases. Med Electron Microsc ; 36 : — The tight junction protein complex undergoes rapid and continuous molecular remodeling at steady state.

J Cell Biol ; : — Rhinovirus infection-induced alteration of tight junction and adherens junction components in human nasal epithelial cells.

Laryngoscope ; : — Claudins create charge-selective channels in the paracellular pathway between epithelial cells. Lastly, similar to plasmodesmata in plant cells, gap junctions are the third type of direct junction found within animal cells. These junctions are channels between adjacent cells that allow for the transport of ions, nutrients, and other substances that enable cells to communicate. Structurally, however, gap junctions and plasmodesmata differ. Gap junctions develop when a set of six proteins called connexins in the plasma membrane arrange themselves in an elongated doughnut-like configuration called a connexon.

Gap junctions are particularly important in cardiac muscle. The electrical signal for the muscle to contract is passed efficiently through gap junctions, which allows the heart muscle cells to contract in tandem.

Learning Objectives Describe the purpose of intercellular junctions in the structure of cells. Key Points Plasmodesmata are intercellular junctions between plant cells that enable the transportation of materials between cells. A tight junction is a watertight seal between two adjacent animal cells, which prevents materials from leaking out of cells. Desmosomes connect adjacent cells when cadherins in the plasma membrane connect to intermediate filaments.

Similar to plasmodesmata, gap junctions are channels between adjacent cells that allow for the transport of ions, nutrients, and other substances. Key Terms plasmodesma : A microscopic channel traversing the cell walls of plant cells and some algal cells, enabling transport and communication between them. Intercellular Junctions The extracellular matrix allows cellular communication within tissues through conformational changes that induce chemical signals, which ultimately transform activities within the cell.

Junctions in Plant Cells In general, long stretches of the plasma membranes of neighboring plant cells cannot touch one another because they are separated by the cell wall that surrounds each cell.



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