Endocytosis of the apical junctional complex: mechanisms and possible roles in regulation of epithelial barriers

Ivanov, Andrei I.; Nusrat, Asma; Parkos, Charles A.

doi:10.1002/bies.20203

Cited by 142 publications

(130 citation statements)

References 93 publications

(175 reference statements)

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“…Previous results suggested that exposure to inflammatory cytokines such as TNF, increases paracellular permeability and induces TJ protein redistribution. 6,9,42,43 Changes in TJ protein localization were assessed by immunofluorescent staining of SB tissue from wild-type and TG mice before and after T cell activation. Occludin was dramatically rearranged from the extracellular membrane to the cytoplasm in wild-type, but not in TG epithelial cells after T cell stimulation ( Figure 4A).…”

Section: Effect Of Epithelial Nf-b Activation On the Redistribution Omentioning

confidence: 99%

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

Tang¹,

Clayburgh

Mittal³

et al. 2010

The American Journal of Pathology

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In inflammatory bowel disease (IBD) , aberrant activation of innate and adaptive immune responses enhances mucosal permeability through mechanisms not completely understood. To examine the role of epithelial nuclear factor (NF-B) in IBD-induced enhanced permeability , epithelial-specific IB␣ mutant (NF-B super repressor) transgenic (TG) mice were generated. NF-kB activation was inhibited in TG mice, relative to wild-type mice , following T cell-mediated immune cell activation using an anti-CD3 monoclonal antibody. Furthermore , epithelial NF-B super repressor protein inhibited diarrhea and blocked changes in transepithelial resistance and transmucosal flux of alexa350 (0.35 kDa) and dextran3000 (3 kDa). In vivo perfusion loop studies in TG mice revealed reversed net water secretion and reduced lumenal flux of different molecular probes (bovine serum albumin, alexa350, and dextran3000). Cell-imaging and immunoblotting of low-density, detergent-insoluble membrane fractions confirmed that tight junction proteins (occludin, claudin-1 and zona occludens-1) are internalized through an NF-B-dependent pathway. Taken together, these data suggest that IBD-associated diarrhea results from NF-B-mediated tight junction protein internalization and increased paracellular permeability. Thus, reduction of epithelial NF-B activation in IBD may repair defects in epithelial barrier function, reduce diarrhea, and limit protein (eg, serum albumin) losses. Epithelial NF-B activation induced by mucosal T cells, therefore, actively plays a role in opening paracellular spaces to promote transmucosal fluid effux into the intestinal lumen.

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Section: Effect Of Epithelial Nf-b Activation On the Redistribution Omentioning

confidence: 99%

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

Tang¹,

Clayburgh

Mittal³

et al. 2010

The American Journal of Pathology

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“…Internalization of junction proteins is one mechanism for temporary or permanent modulation of cell-cell adhesion (reviewed in Bryant and Stow, 2004;D'Souza-Schorey, 2005;Ivanov et al, 2005). A number of cell-cell junction proteins have been demonstrated to internalize in response to various physiological stimuli.…”

Section: Introductionmentioning

confidence: 99%

EGF induces macropinocytosis and SNX1-modulated recycling of E-cadherin

Bryant

Kerr

Hammond

et al. 2007

Journal of Cell Science

172

195

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In epithelia, junction proteins are endocytosed for modulation of cell-cell adhesion and cell polarity. In response to growth factors, the cell-cell adhesion protein E-cadherin is internalized from the cell surface with degradation or recycling as potential fates. However, the cellular machinery involved in cadherin internalization and recycling remains controversial. Here we investigated EGF-induced E-cadherin internalization. EGF stimulation of MCF-7 cells resulted in Rac1-modulated macropinocytosis of the E-cadherin-catenin complex into endosomal compartments that colocalized with EEA1 and the sorting nexin, SNX1. Depletion of cellular SNX1 levels by siRNA resulted in increased intracellular accumulation and turnover of E-cadherin internalized from the cell surface in response to EGF. Moreover, SNX1 was also required for efficient recycling of internalized E-cadherin and re-establishment of epithelial adhesion. Together, these findings demonstrate a role for SNX1 in retrieval of E-cadherin from a degradative endosomal pathway and in membrane trafficking pathways that regulate E-cadherin recycling.

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“…[18][19][20] This mechanism also provides the efficient means for restructuring junctional complexes at the TJ-barrier by perturbing its permeability without requiring de novo protein synthesis. 18 For instance, it is suggested that intercellular movement is achieved by coendocytosis of apposing TJ-integral membrane proteins into the adjacent cells in a study using mouse Eph4 cells in vitro. 19 Besides, there is growing evidence that the "leaky" intestinal epithelia in chronic disorders is mediated by abnormal internalization of TJ-integral membrane proteins via endocytosis.…”

Section: The Concept Of Endocytosis In Btb Dynamicsmentioning

confidence: 99%

“…This apparently is in contrast to other blood-tissue barriers (e.g., blood-brain and blood-retina barriers), even though they are suggested to be dynamic in nature. 18 Unlike the BTB, these blood-tissue barriers do not undergo such drastic restructuring to facilitate the migration of preleptotene spermatocytes which are 10-15 μm in diameter. Besides, except for stage VIII of the epithelial cycle, the BTB remains closed to limit the entry of preleptotene spermatocytes into the adluminal compartment.…”

Section: Es and Aj)mentioning

confidence: 99%

Cross-Talk between Tight and Anchoring Junctions—Lesson from the Testis

Yan

Mruk

Lee

et al. 2009

Advances in Experimental Medicine and Biology

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Spermatogenesis takes place in the seminiferous tubules in adult testes such as rats, in which developing germ cells must traverse the seminiferous epithelium while spermatogonia (2n, diploid) undergo mitotic and meiotic divisions, and differentiate into elongated spermatids (1n, haploid). It is conceivable that this event involves extensive junction restructuring particularly at the blood-testis barrier (BTB, a structure that segregates the seminiferous epithelium into the basal and the adluminal compartments) that occurs at stages VII-VIII of the seminiferous epithelial cycle. As such, cross-talk between tight (TJ) and anchoring junctions [e.g., basal ectoplasmic specialization (basal ES), adherens junction (AJ), desmosome-like junction (DJ)] at the BTB must occur to coordinate the transient opening of the BTB to facilitate preleptotene spermatocyte migration. Interestingly, while there are extensively restructuring at the BTB during the epithelial cycle, the immunological barrier function of the BTB must be maintained without disruption even transiently. Recent studies using the androgen suppression and Adjudin models have shown that anchoring junction restructuring that leads to germ cell loss from the seminiferous epithelium also promotes the production of AJ (e.g., basal ES) proteins (such as N-cadherins, catenins) at the BTB site. We postulate the testis is using a similar mechanism during spermatogenesis at stage VIII of the epithelial cycle that these induced basal ES proteins, likely form a "patch" surrounding the BTB, transiently maintain the BTB integrity while TJ is "opened", such as induced by TGF-b3 or TNFa, to facilitate preleptotene spermatocyte migration. However, in other stages of the epithelial cycle other than VII and VIII when the BTB remains "closed" (for ~10 days), anchoring junctions (e.g., AJ, DJ, and apical ES) restructuring continues to facilitate germ cell movement. Interestingly, the mechanism(s) that governs this communication between TJ and anchoring junction (e.g., basal ES and AJ) in the testis has remained obscure until recently. Herein, we provide a critical review based on the recently available data regarding the cross-talk between TJ and anchoring junction to allow simultaneous maintenance of the BTB and germ cell movement across the seminiferous epithelium.

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Endocytosis of the apical junctional complex: mechanisms and possible roles in regulation of epithelial barriers

Cited by 142 publications

References 93 publications

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

EGF induces macropinocytosis and SNX1-modulated recycling of E-cadherin

Cross-Talk between Tight and Anchoring Junctions—Lesson from the Testis

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