The unique-5 and -6 motifs of ZO-1 regulate tight junction strand localization and scaffolding properties

Mol Biol Cell. 2007 Mar;18(3):721-31. doi: 10.1091/mbc.e06-08-0764. Epub 2006 Dec 20.


The proper cellular location and sealing of tight junctions is assumed to depend on scaffolding properties of ZO-1, a member of the MAGUK protein family. ZO-1 contains a conserved SH3-GUK module that is separated by a variable region (unique-5), which in other MAGUKs has proven regulatory functions. To identify motifs in ZO-1 critical for its putative scaffolding functions, we focused on the SH3-GUK module including unique-5 (U5) and unique-6 (U6), a motif immediately C-terminal of the GUK domain. In vitro binding studies reveal U5 is sufficient for occludin binding; U6 reduces the affinity of this binding. In cultured cells, U5 is required for targeting ZO-1 to tight junctions and removal of U6 results in ectopically displaced junction strands containing the modified ZO-1, occludin, and claudin on the lateral cell membrane. These results provide evidence that ZO-1 can control the location of tight junction transmembrane proteins and reveals complex protein binding and targeting signals within its SH3-U5-GUK-U6 region. We review these findings in the context of regulated scaffolding functions of other MAGUK proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • Dogs
  • Freeze Fracturing
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Occludin
  • Peptides / metabolism
  • Phosphoproteins / chemistry*
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Transport
  • Tight Junctions / metabolism*
  • Transgenes
  • Zonula Occludens-1 Protein
  • src Homology Domains


  • Membrane Proteins
  • Occludin
  • Peptides
  • Phosphoproteins
  • Zonula Occludens-1 Protein