Par-3 controls tight junction assembly through the Rac exchange factor Tiam1
- PMID: 15723052
- DOI: 10.1038/ncb1226
Par-3 controls tight junction assembly through the Rac exchange factor Tiam1
Abstract
The par (partitioning-defective) genes express a set of conserved proteins that function in polarization and asymmetric cell division. Par-3 has multiple protein-interaction domains, and associates with Par-6 and atypical protein kinase C (aPKC). In Drosophila, Par-3 is essential for epithelial cell polarization. However, its function in mammals is unclear. Here we show that depletion of Par-3 in mammalian epithelial cells profoundly disrupts tight junction assembly. Expression of a carboxy-terminal fragment plus the third PDZ domain of Par-3 partially rescues junction assembly, but neither Par-6 nor aPKC binding is required. Unexpectedly, Rac is constitutively activated in cells lacking Par-3, and the assembly of tight junctions is efficiently restored by a dominant-negative Rac mutant. The Rac exchange factor Tiam1 (ref. 7) binds directly to the carboxy-terminal region of Par-3, and knockdown of Tiam1 enhances tight junction formation in cells lacking Par-3. These results define a critical function for Par-3 in tight junction assembly, and reveal a novel mechanism through which Par-3 engages in the spatial regulation of Rac activity and establishment of epithelial polarity.
Comment in
-
Pars and polarity: taking control of Rac.Nat Cell Biol. 2005 Mar;7(3):205-7. doi: 10.1038/ncb0305-205. Nat Cell Biol. 2005. PMID: 15738967 No abstract available.
Similar articles
-
The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex.J Cell Biol. 2005 Sep 26;170(7):1029-37. doi: 10.1083/jcb.200502129. J Cell Biol. 2005. PMID: 16186252 Free PMC article.
-
Caspase-mediated cleavage of the TIAM1 guanine nucleotide exchange factor during apoptosis.Cell Growth Differ. 2001 Dec;12(12):603-11. Cell Growth Differ. 2001. PMID: 11751455
-
Interaction between PAR-3 and the aPKC-PAR-6 complex is indispensable for apical domain development of epithelial cells.J Cell Sci. 2009 May 15;122(Pt 10):1595-606. doi: 10.1242/jcs.043174. Epub 2009 Apr 28. J Cell Sci. 2009. PMID: 19401335
-
Tiam1 takes PARt in cell polarity.Trends Cell Biol. 2006 Jun;16(6):308-16. doi: 10.1016/j.tcb.2006.04.001. Epub 2006 May 2. Trends Cell Biol. 2006. PMID: 16650994 Review.
-
The interdependence of the Rho GTPases and apicobasal cell polarity.Small GTPases. 2014;5(2):10. doi: 10.4161/21541248.2014.973768. Small GTPases. 2014. PMID: 25469537 Free PMC article. Review.
Cited by
-
PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion.Cancer Res. 2015 Apr 1;75(7):1287-97. doi: 10.1158/0008-5472.CAN-14-2444. Cancer Res. 2015. PMID: 25833829 Free PMC article.
-
PARD3 induces TAZ activation and cell growth by promoting LATS1 and PP1 interaction.EMBO Rep. 2015 Aug;16(8):975-85. doi: 10.15252/embr.201439951. Epub 2015 Jun 26. EMBO Rep. 2015. PMID: 26116754 Free PMC article.
-
The signaling adaptor GAB1 regulates cell polarity by acting as a PAR protein scaffold.Mol Cell. 2012 Aug 10;47(3):469-83. doi: 10.1016/j.molcel.2012.06.037. Mol Cell. 2012. PMID: 22883624 Free PMC article.
-
Par3 regulates invasion of pancreatic cancer cells via interaction with Tiam1.Clin Exp Med. 2016 Aug;16(3):357-65. doi: 10.1007/s10238-015-0365-2. Epub 2015 Jun 18. Clin Exp Med. 2016. PMID: 26084985
-
Polarization of Drosophila neuroblasts during asymmetric division.Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a001388. doi: 10.1101/cshperspect.a001388. Cold Spring Harb Perspect Biol. 2009. PMID: 20066083 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
