Setting up a selective barrier at the apical junction complex
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:
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of special interest
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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.
References (43)
- et al.
Claudin-based barrier in simple and stratified cellular sheets
Curr Opin Cell Biol
(2002) Claudin complexities at the apical junctional complex
Nat Cell Biol
(2003)- et al.
Dynamic behavior of paired claudin strands within apposing plasma membranes
Proc Natl Acad Sci U S A
(2003) - et al.
Composition and function of PDZ protein complexes during cell polarization
Am J Physiol Renal Physiol
(2003) - et al.
Direct interaction of two polarity complexes implicated in epithelial tight junction assembly
Nat Cell Biol
(2003) - et al.
Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas
Clin Cancer Res
(2003) - et al.
Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption
Science
(1999) - et al.
Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT
Nat Genet
(2003) - et al.
Molecular complexity of vertebrate tight junctions
Mol Membr Biol
(2002) Claudins and epithelial paracellular transport: the end of the beginning
Curr Opin Nephrol Hypertens
(2003)
Epithelial cell adhesion and the regulation of gene expression
Trends Cell Biol
Claudins create charge-selective channels in the paracellular pathway between epithelial cells
Am J Physiol Cell Physiol
Claudin-8 interacts with multi-PDZ domain protein 1 (MUPP1) and reduces paracellular conductance in epithelial cells
Cell Mol Biol (Noisy-le-grand)
Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation
J Biol Chem
Channels in epithelial cell membranes and junctions
Fed Proc
Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice
J Cell Biol
Adherens junctions: new insight into assembly, modulation and function
Bioessays
Epithelial cell polarity and cell junctions in Drosophila
Annu Rev Genet
Stages in the assembly of pleated and smooth septate junctions in developing insect embryos
J Cell Sci
The claudin-like megatrachea is essential in septate junctions for the epithelial barrier function in Drosophila
Dev Cell
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