Molecular Biology of the Cell Sign up for new MBC in Press e-TOCs!

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E06-08-0764 on December 20, 2006

Vol. 18, Issue 3, 721-731, March 2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
E06-08-0764v1
18/3/721    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fanning, A. S.
Right arrow Articles by Anderson, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fanning, A. S.
Right arrow Articles by Anderson, J. M.

The Unique-5 and -6 Motifs of ZO-1 Regulate Tight Junction Strand Localization and Scaffolding PropertiesFormula

Alan S. Fanning*, Brent P. Little{dagger}, Christoph Rahner{ddagger}, Darkhan Utepbergenov§, Zenta Walther||, and James M. Anderson*

*Department of Cell and Molecular Physiology and §School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7545; {dagger}Department of Diagnostic Radiology, Albert Einstein College of Medicine, Bronx, NY 10467; and Departments of {ddagger}Cell Biology and ||Pathology, Yale University School of Medicine, New Haven, CT 06510

Submitted August 29, 2006; Revised November 17, 2006; Accepted December 1, 2006
Monitoring Editor: Ben Margolis

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.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-08-0764) on December 20, 2006.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Alan S. Fanning (alan.fanning{at}med.unc.edu)




This article has been cited by other articles:


Home page
 J. Cell Biol.Home page
L. Shen, C. R. Weber, and J. R. Turner
The tight junction protein complex undergoes rapid and continuous molecular remodeling at steady state
J. Cell Biol., May 19, 2008; 181(4): 683 - 695.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. S. Fanning, M. F. Lye, J. M. Anderson, and A. Lavie
Domain Swapping within PDZ2 Is Responsible for Dimerization of ZO Proteins
J. Biol. Chem., December 28, 2007; 282(52): 37710 - 37716.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.