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The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton.

The tight junction protein ZO-1 belongs to a family of multidomain proteins known as the membrane-associated guanylate kinase homologs (MAGUKs). ZO-1 has been demonstrated to interact with the transmembrane protein occludin, a second tight junction-specific MAGUK, ZO-2, and F-actin, although the nature and functional significance of these interactions is poorly understood. To further elucidate the role of ZO-1 within the epithelial tight junction, we have introduced epitope-tagged fragments of ZO-1 into cultured MDCK cells and identified domains critical for the interaction with ZO-2, occludin, and F-actin. A combination of in vitro and in vivo binding assays indicate that both ZO-2 and occludin interact with specific domains within the N-terminal (MAGUK-like) half of ZO-1, whereas the unique proline-rich C-terminal half of ZO-1 cosediments with F-actin. Consistent with these observations, we found that a construct encoding the N-terminal half of ZO-1 is specifically associated with tight junctions, whereas the unique C-terminal half of ZO-1 is distributed over the entire lateral surface of the plasma membrane and other actin-rich structures. In addition, we have identified a 244-amino acid domain within the N-terminal half of ZO-1, which is required for the stable incorporation of ZO-1 into the junctional complex of polarized MDCK cells. These observations suggest that one functional role of ZO-1 is to organize components of the tight junction and link them to the cortical actin cytoskeleton.

Pubmed ID: 9792688


  • Fanning AS
  • Jameson BJ
  • Jesaitis LA
  • Anderson JM


The Journal of biological chemistry

Publication Data

November 6, 1998

Associated Grants

  • Agency: NCI NIH HHS, Id: CA66263
  • Agency: NIDDK NIH HHS, Id: DK34989
  • Agency: NIDDK NIH HHS, Id: DK45134

Mesh Terms

  • Actins
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cytoskeleton
  • DNA Primers
  • Dogs
  • Membrane Proteins
  • Occludin
  • Phosphoproteins
  • Zonula Occludens-1 Protein