Junctional trafficking and epithelial morphogenesis

Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Current opinion in genetics & development (Impact Factor: 7.57). 07/2009; 19(4):350-6. DOI: 10.1016/j.gde.2009.04.011
Source: PubMed


Epithelial monolayers are major determinants of three-dimensional tissue organization and provide the structural foundation for the body plan and all of its component organs. Epithelial cells are connected by junctional complexes containing the cell adhesion molecule E-cadherin. Adherens junctions mediate stable cohesion between cells but must be actively reorganized to allow tissue remodeling during development. Recent studies demonstrate that junctional proteins are dynamically turned over at the cell surface, even in cells that do not appear to be moving. The redistribution of E-cadherin through spatially regulated endocytosis and exocytosis contributes to cell adhesion, cell polarity, and cell rearrangement. Here we describe recent progress in understanding the roles of the vesicle transport machinery in regulating cell adhesion and junctional dynamics during epithelial morphogenesis in vivo.

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    • "Our results demonstrated that in the SAP group, the permeability of the intestinal barrier increased with the decline of aSNAP expression in intestinal epithelial cells and in parallel with the changes in occludin expression. At the same time, a large body of evidence suggests that the remodeling of TJs is regulated by vesicle trafficking, during which the disassembly and reassembly steps are mediated by the endocytosis and exocytosis of junctional proteins [11] [42] [43]. In the study, the downregulation of aSNAP led to decreased expression of occluding in vitro. "
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    ABSTRACT: Background and objective: Intestinal barrier damage is an important event during the occurrence and progression of severe acute pancreatitis. The expression of occludin, one of the main components of the intestinal barrier proteins, is regulated by various factors related to intestinal barrier formation and the remodeling process. The αSNAP, as a novel membrane protein, is ubiquitously expressed in intestinal epithelial cells. This study aimed to investigate the role of αSNAP in acute pancreatitis and the relationship between occludin and αSNAP. Methods: Mild and severe acute pancreatitis models were established by retrograde injections of 0.5% and 3.8% sodium taurocholate solutions, respectively, into rat pancreaticobiliary ducts. The animals were killed at 1, 2, and 3 days after the injection, and the pathological changes of the pancreas and intestinal mucosa, the changes in intestinal permeability, and the protein expression of occludin and αSNAP were assessed. Cultured epithelial IEC-6 cells were further infected with lentiviral αSNAP shRNA, cell apoptosis was determined with flow cytometry (FCM), and any changes in occludin expression were detected by Western blotting and immunofluorescent staining. Results: This pathologic study of a rat acute pancreatitis model indicated pancreatic tissue necrosis and inflammatory cell infiltration; the intestinal villi in the severe acute pancreatitis (SAP) group demonstrated edema, lodging, atrophy, and intestinal epithelial cell necrosis, and shedding. The intestinal permeability in rats with pancreatitis increased significantly. The SAP group showed significantly increased levels of serum TNF-α and endotoxins. The results of immunofluorescent staining and Western blotting revealed that compared with the SO (sham operation) and MAP (mild acute pancreatitis) groups, the SAP group displayed significantly downregulated protein expressions of αSNAP and occludin in the intestinal epithelial cells. After the lentiviral transduction of αSNAP shRNA, apoptosis in IEC-6 cells was drastically increased, whereas the expression of occludin was decreased significantly. Conclusion: The downregulated expression of αSNAP in intestinal epithelial cells leads to reduced occludin expression and enhanced apoptosis of intestinal epithelial cells. Hence, the permeability of the intestinal barrier may be increased in a severe acute pancreatitis model.
    Full-text · Article · Sep 2014 · Pancreatology
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    • "— Does internalization of protrusions involve exploitation of host endocytic pathways that normally control junctional integrity? Apical junctions are sites of endocytosis, as well as exocytosis [146,173,174]. Constitutive endocytosis of TJ and AJ components is thought to be involved in epithelial tissue homeostasis [146]. "
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    ABSTRACT: Several bacterial pathogens, including Listeria monocytogenes, Shigella flexneri and Rickettsia spp., have evolved mechanisms to actively spread within human tissues. Spreading is initiated by the pathogen-induced recruitment of host filamentous (F)-actin. F-actin forms a tail behind the microbe, propelling it through the cytoplasm. The motile pathogen then encounters the host plasma membrane, forming a bacterium-containing protrusion that is engulfed by an adjacent cell. Over the past two decades, much progress has been made in elucidating mechanisms of F-actin tail formation. Listeria and Shigella produce tails of branched actin filaments by subverting the host Arp2/3 complex. By contrast, Rickettsia forms tails with linear actin filaments through a bacterial mimic of eukaryotic formins. Compared with F-actin tail formation, mechanisms controlling bacterial protrusions are less well understood. However, recent findings have highlighted the importance of pathogen manipulation of host cell–cell junctions in spread. Listeria produces a soluble protein that enhances bacterial protrusions by perturbing tight junctions. Shigella protrusions are engulfed through a clathrin-mediated pathway at ‘tricellular junctions’—specialized membrane regions at the intersection of three epithelial cells. This review summarizes key past findings in pathogen spread, and focuses on recent developments in actin-based motility and the formation and internalization of bacterial protrusions.
    Full-text · Article · Jul 2013 · Open Biology
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    • "During morphogenesis, elongation of epithelial sheets or tubes can be achieved by planar-polarised cell intercalation, involving the oriented making and breaking of intercellular contacts (reviewed by Keller, 2002; Bertet and Lecuit, 2009; Affolter et al., 2009; Vichas and Zallen, 2011). The mechanisms by which cells can remodel their junctional contacts are still poorly understood, but one possibility is that this occurs via localised endocytic trafficking of E-cad (reviewed by Wirtz-Peitz and Zallen, 2009). "
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    ABSTRACT: Polarised tissue elongation during morphogenesis involves cells within epithelial sheets or tubes making and breaking intercellular contacts in an oriented manner. Growing evidence suggests that cell adhesion can be modulated by endocytic trafficking of E-cadherin (E-cad), but how this process can be polarised within individual cells is poorly understood. The Frizzled (Fz)-dependent core planar polarity pathway is a major regulator of polarised cell rearrangements in processes such as gastrulation, and has also been implicated in regulation of cell adhesion through trafficking of E-cad; however, it is not known how these functions are integrated. We report a novel role for the core planar polarity pathway in promoting cell intercalation during tracheal tube morphogenesis in Drosophila embryogenesis, and present evidence that this is due to regulation of turnover and levels of junctional E-cad by the guanine exchange factor RhoGEF2. Furthermore, we show that core pathway activity leads to planar-polarised recruitment of RhoGEF2 and E-cad turnover in the epidermis of both the embryonic germband and the pupal wing. We thus reveal a general mechanism by which the core planar polarity pathway can promote polarised cell rearrangements.
    Full-text · Article · Jan 2013 · Development
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