Setting up a selective barrier at the apical junction complex

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Abstract

Across the animal kingdom the apical junction complex of epithelial cells creates both a permeability barrier and cell polarity. Although based on overlapping and evolutionarily conserved proteins, the cell–cell contacts of nematodes, flies and mammals appear to differ in morphology and functional organization. Emerging evidence shows that the selective pore-like properties of vertebrate and invertebrate barriers are created by the claudin family. Similarly, assembly of the barriers requires a conserved set of polarity-generating protein complexes, particularly the PAR protein complexes.

Introduction

The defining characteristics of epithelia include their ability to create selective barriers between tissue spaces and to generate polarity of cellular structure and function. The first characteristic allows tissues to regulate paracellular movements of solutes down their electro-osmotic gradients. The second allows the apical and basolateral membrane surfaces to recognize signals directionally or to transport material across the epithelium. The apical junctional complex, which is composed of the tight junction (TJ) and the adherens junction (AJ), is intimately involved in both permeability and polarity. In this short review we will focus on advances in understanding control of the paracellular barrier by the claudin family of transmembrane proteins [1]. We briefly highlight the similarities and differences across phyla in creating the barrier and polarity. Recent excellent reviews have focused on the molecular components 1.•, 2. and regulation 3., 4. of TJs.

Section snippets

Claudins create the barrier and its selective pore properties

The paracellular–TJ pathway across epithelia behaves like a barrier perforated with selective pores [3]. Together with transcellular transport (e.g. channels, pumps, carriers and exchangers), tissue-specific TJ characteristics determine the overall epithelial absorption and secretion. The defining ultrastructural features of vertebrate TJs are strands of transmembrane protein particles that adhere to similar strands on adjacent cells to create a series of barriers in the paracellular pathway [1

Structural and functional zones along the apical junctional complexes

From nematodes to flies to mammals, the apical junctional complex controls permeability, adhesion, cell growth and polarity. Despite this, its morphological details vary among the groups and their protein sets only partially overlap (reviewed in 12., 13.; see Figure 2). In vertebrate epithelial cells, the apical-most contact is the barrier-forming TJ, followed by the cadherin-based AJ (Figure 2). In Drosophila, the complex begins at the apical end with the so-called apical marginal zone,

Claudins in Drosophila

In Diptera, the epithelial barrier is functionally located at septate junctions, which are ultrastructurally very distinct from vertebrate TJs [14]. Further obscuring their comparison, most of the Drosophila homologs of TJ proteins were previously documented to be in the AJ or in marginal zone (reviewed in [15••]). Now, the recent demonstration 15.••, 16.•• of the presence of two claudins in septate junctions provides the first definitive evidence of a common molecular basis for the barrier in

Claudins in C. elegans

Although apical junctions in C. elegans appear as single electron-dense structures, immunofluorescent analysis of various proteins reveals subdomains, with polarity proteins and cadherin/catenins (HMR-1/HMP-1) localized apical to AJM-1 and DLG-1 [17]. Provocatively, Tsukita and colleagues [18••] recently identified a potential new intercellular junction apical to the AJ. Although clearly not a TJ, this structure is characterized by more closely opposed plasma membranes than are seen in AJs; its

Barrier biogenesis and conserved polarity protein complexes

In both vertebrates and invertebrates, cell–cell junctions are associated with a cytosolic plaque that is enriched in multi-domain scaffolding proteins, including the ZO proteins (ZO-1, -2 and 3), MUPP-1 and MAGI (reviewed in [2]). Although it has long been speculated that interactions with these cytosolic proteins regulate the localization and function of the transmembrane barrier proteins, there is little direct evidence. Early studies suggested that transmembrane proteins like claudin and

Are tight junctions involved in differentiation and cell proliferation?

Theoretically, all junctions provide an opportunity for transfer of information across the plasma membrane. Cell differentiation and growth are often controlled by engaging molecules on adjacent cells or matrix. Surprisingly, until very recently there has been little suggestion that TJs influence differentiation and proliferation. Some evidence remains descriptive and we focus on a potential role for ZO-1 and claudin.

The most compelling example linking TJs with cell growth involves ZO-1. Balda

Conclusions

In spite of the varying morphologic features of the apical junctional complexes in different phyla, claudins appear to play a central role in creating all their barriers and selective properties. The machinery used to establish cellular polarity is also conserved across phyla and likewise is required to establish a competent paracellular barrier. Despite commonalties, there are curious differences at the detailed level between the different systems and continued comparison of all models is

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • of special interest

  • ••

    of outstanding interest

Acknowledgements

The authors thank the State of North Carolina, the Broad Medical Research Program of the Eli and Edythe L. Broad Foundation and the National Institutes of Health (DK61397, DK34134) for support of their research. We thank Dr Jeffery Hardin (University of Wisconsin) for his insights regarding cell junctions in nematodes.

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