Zonula occludens-1 and -2 are cytosolic scaffolds that regulate the assembly of cellular junctions - PubMed (original) (raw)

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Zonula occludens-1 and -2 are cytosolic scaffolds that regulate the assembly of cellular junctions

Alan S Fanning et al. Ann N Y Acad Sci. 2009 May.

Abstract

The integrity of the tight junction barrier in epithelial and endothelial cells is critical to human health, but we still lack a detailed mechanistic knowledge of how the barrier is formed during development or responds to pathological and pharmacological insults. This limits our understanding of barrier dysfunction in disease and slows the development of therapeutic strategies. Recent studies confirm the long-maintained but previously unsupported view that the zonula occludens (ZO) proteins ZO-1 and ZO-2 are critical determinants of barrier formation. However, ZO proteins can also be components of adherens junctions, and recent studies suggest that ZO proteins may also promote the assembly and function of these junctions during epithelial morphogenesis. We review these studies and outline several recent observations that suggest that one role of ZO proteins is to regulate cytoskeletal dynamics at cell junctions. Finally, we propose a model by which the functional activities of ZO proteins in the adherens junction and tight junction are differentiated by a novel regulatory motif known as the U6 or acidic motif.

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Conflict of interest statement

Conflicts of Interest

The authors declare no conflicts of interest.

Figures

Figure 1

Figure 1

Zonula occludens (ZO) proteins are multidomain scaffolds required for tight junction (TJ) assembly. Protein ligands and their binding sites on ZO-1 (top), ZO-2, and ZO-3. The functional roles of different regions are indicated (bottom). See text for details. ABR, actin-binding region; ARVCF, armadillo repeat gene deleted in velo-cardiofacial syndrome; CaM, calmodulin; GUK, guanylate kinase-like domain; PDZ, PSD-95/discs-large/zonula occludens-1 domain; PLCB3, phospholipase-C B3; SAF-B, scaffold attachment factor-B; SH3, Src Homology-3 domain; ZAK, zonula occludens kinase; ZONAB, ZO-1-associated nucleic acid binding protein; α, β, and ZU5, alternatively spliced domains of unknown function.

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