![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 17, Issue 4, 1922-1932, April 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908-0577
Submitted July 19, 2005;
Revised January 6, 2006;
Accepted January 12, 2006
Monitoring Editor: Asma Nusrat
Zonula occludens (ZO)-1 was the first tight junction protein to be cloned and has been implicated as an important scaffold protein. It contains multiple domains that bind a diverse set of junction proteins. However, the molecular functions of ZO-1 and related proteins such as ZO-2 and ZO-3 have remained unclear. We now show that gene silencing of ZO-1 causes a delay of 
3 h in tight junction formation in Madin-Darby canine kidney (MDCK) epithelial cells, but mature junctions seem functionally normal even in the continuing absence of ZO-1. Depletion of ZO-2, cingulin, or occludin, proteins that can interact with ZO-1, had no discernible effects on tight junctions. Rescue of junction assembly using murine ZO-1 mutants demonstrated that the ZO-1 C terminus is neither necessary nor sufficient for normal assembly. Moreover, mutation of the PDZ1 domain did not block rescue. However, point mutations in the Src homology 3 (SH3) domain almost completely prevented rescue. Surprisingly, the isolated SH3 domain of ZO-1 could also rescue junction assembly. These data reveal an unexpected function for the SH3 domain of ZO-1 in regulating tight junction assembly in epithelial cells and show that cingulin, occludin, or ZO-2 are not limiting for junction assembly in MDCK monolayers.
Abbreviations used: GUK, guanylate kinase-like; PDZ, PSD-95, Discs large, ZO-1; YFP, yellow fluorescent protein; ZO-1, zonula occludens-1.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Ian G. Macara (igm9c{at}virginia.edu).
This article has been cited by other articles:
|
|
 |
|
  S. Tuomi, A. Mai, J. Nevo, J. O. Laine, V. Vilkki, T. J. Ohman, C. G. Gahmberg, P. J. Parker, and J. Ivaska PKC{varepsilon} Regulation of an {alpha}5 Integrin-ZO-1 Complex Controls Lamellae Formation in Migrating Cancer Cells Sci. Signal., June 30, 2009; 2(77): ra32 - ra32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Brady, J. K. Alan, J. P. Madigan, A. S. Fanning, and A. D. Cox The Transforming Rho Family GTPase Wrch-1 Disrupts Epithelial Cell Tight Junctions and Epithelial Morphogenesis Mol. Cell. Biol., February 15, 2009; 29(4): 1035 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yamazaki, K. Umeda, M. Wada, S. Nada, M. Okada, S. Tsukita, and S. Tsukita ZO-1- and ZO-2-Dependent Integration of Myosin-2 to Epithelial Zonula Adherens Mol. Biol. Cell, September 1, 2008; 19(9): 3801 - 3811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sabath, H. Negoro, S. Beaudry, M. Paniagua, S. Angelow, J. Shah, N. Grammatikakis, A. S. L. Yu, and B. M. Denker G{alpha}12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly J. Cell Sci., March 15, 2008; 121(6): 814 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, P. J. Kausalya, D. C. Y. Phua, S. M. Ali, Z. Hossain, and W. Hunziker Early Embryonic Lethality of Mice Lacking ZO-2, but Not ZO-3, Reveals Critical and Nonredundant Roles for Individual Zonula Occludens Proteins in Mammalian Development Mol. Cell. Biol., March 1, 2008; 28(5): 1669 - 1678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Matter and M. S. Balda Epithelial tight junctions, gene expression and nucleo-junctional interplay J. Cell Sci., May 1, 2007; 120(9): 1505 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Blikslager, A. J. Moeser, J. L. Gookin, S. L. Jones, and J. Odle Restoration of Barrier Function in Injured Intestinal Mucosa Physiol Rev, April 1, 2007; 87(2): 545 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Fanning, B. P. Little, C. Rahner, D. Utepbergenov, Z. Walther, and J. M. Anderson The Unique-5 and -6 Motifs of ZO-1 Regulate Tight Junction Strand Localization and Scaffolding Properties Mol. Biol. Cell, March 1, 2007; 18(3): 721 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. Capaldo and I. G. Macara Depletion of E-Cadherin Disrupts Establishment but Not Maintenance of Cell Junctions in Madin-Darby Canine Kidney Epithelial Cells Mol. Biol. Cell, January 1, 2007; 18(1): 189 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Otani, T. Ichii, S. Aono, and M. Takeichi Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells J. Cell Biol., October 9, 2006; 175(1): 135 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sharma, S. H. Low, S. Misra, B. Pallavi, and T. Weimbs Apical targeting of syntaxin 3 is essential for epithelial cell polarity J. Cell Biol., June 19, 2006; 173(6): 937 - 948. [Abstract] [Full Text] [PDF]
|
|
