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

Alan S. Fanning, Brent P. Little, Christoph Rahner, Darkhan Utepbergenov, Zenta Walther, James M. Anderson

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)721-731
Number of pages11
JournalMolecular Biology of the Cell
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

Fingerprint

Guanylate Kinases
Occludin
Tight Junctions
Claudin-1
Tight Junction Proteins
Protein Transport
Protein Binding
Cultured Cells
Cell Membrane

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

The unique-5 and -6 motifs of ZO-1 regulate tight junction strand localization and scaffolding properties. / Fanning, Alan S.; Little, Brent P.; Rahner, Christoph; Utepbergenov, Darkhan; Walther, Zenta; Anderson, James M.

In: Molecular Biology of the Cell, Vol. 18, No. 3, 03.2007, p. 721-731.

Research output: Contribution to journalArticle

Fanning, Alan S. ; Little, Brent P. ; Rahner, Christoph ; Utepbergenov, Darkhan ; Walther, Zenta ; Anderson, James M. / The unique-5 and -6 motifs of ZO-1 regulate tight junction strand localization and scaffolding properties. In: Molecular Biology of the Cell. 2007 ; Vol. 18, No. 3. pp. 721-731.
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