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PMID: 19538295 Published · ppublish English Journal Article Review

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

Annals of the New York Academy of Sciences ·Vol. 1165 ·2009-05-00 ·Pages 113-20

Fanning AS, Anderson JM

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.

MeSH Terms
Amino Acid Motifs Animals Cytosol/metabolism Epithelial Cells/metabolism Humans Intercellular Junctions/metabolism Membrane Proteins/metabolism Phosphoproteins/metabolism Protein Structure, Tertiary Tight Junctions/metabolism Zonula Occludens-1 Protein Zonula Occludens-2 Protein
Chemicals
Membrane Proteins Phosphoproteins TJP1 protein, human TJP2 protein, human Zonula Occludens-1 Protein Zonula Occludens-2 Protein
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Fanning Alan S
The Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545, USA. alan_fanning@med.unc.edu
Anderson James M
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Article Info
Journal
Annals of the New York Academy of Sciences
Abbr.
Ann N Y Acad Sci
ISSN
1749-6632
DOI
10.1111/j.1749-6632.2009.04440.x
Email
alan_fanning@med.unc.edu
Published
2009-05-00
Pages
113-20
Language
English
Region
United States
NLM ID
7506858
PMCID
PMC3759978
Subset
IM
Grants
NIDDK NIH HHS · R01 DK061397 · United States
External Links
PubMed source DOI: 10.1111/j.1749-6632.2009.04440.x PMC Full Text View journal details
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