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• W2000709179 abstract "Epithelial cells display apical-basal polarity, and the apical surface is segregated from the basolateral membranes by a barrier called the tight junction (TJ). TJs are constructed from transmembrane proteins that form cell-cell contacts—claudins, occludin, and junctional adhesion molecule (JAM)—plus peripheral proteins such as ZO-1 [1Cereijido M. Valdes J. Shoshani L. Contreras R.G. Role of tight junctions in establishing and maintaining cell polarity.Annu. Rev. Physiol. 1998; 60: 161-177Crossref PubMed Scopus (210) Google Scholar, 2Mitic L.L. Anderson J.M. Molecular architecture of tight junctions.Annu. Rev. Physiol. 1998; 60: 121-142Crossref PubMed Scopus (601) Google Scholar]. The Par proteins (partitioning-defective) Par3 and Par6, plus atypical protein kinase C (aPKC) function in the formation or maintenance of TJs [3Lin D. Edwards A.S. Fawcett J.P. Mbamalu G. Scott J.D. Pawson T. A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity.Nat. Cell Biol. 2000; 2: 540-547Crossref PubMed Scopus (47) Google Scholar, 4Joberty G. Petersen C. Gao L. Macara I.G. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42.Nat. Cell Biol. 2000; 2: 531-539Crossref PubMed Scopus (724) Google Scholar, 5Suzuki A. Yamanaka T. Hirose T. Manabe N. Mizuno K. Shimizu M. Akimoto K. Izumi Y. Ohnishi T. Ohno S. Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures.J. Cell Biol. 2001; 152: 1183-1196Crossref PubMed Scopus (371) Google Scholar] and more generally in metazoan cell polarity establishment [6Petronczki M. Knoblich J.A. DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila.Nat. Cell Biol. 2001; 3: 43-49Crossref PubMed Scopus (314) Google Scholar, 7Qiu R.G. Abo A. Steven Martin G. A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation.Curr. Biol. 2000; 10: 697-707Abstract Full Text Full Text PDF PubMed Scopus (226) Google Scholar]. Par6 contains a PDZ domain and a partial CRIB (Cdc42/Rac interactive binding) domain and binds the small GTPase Cdc42. Here, we show that Par6 inhibits TJ assembly in MDCK II epithelial cells after their disruption by Ca2+ depletion but does not inhibit adherens junction (AJ) formation. Transepithelial resistance and paracellular diffusion assays confirmed that assembly of functional TJs is delayed by Par6 overexpression. Strikingly, the isolated, N-terminal fragment of PKCζ, which binds Par6, also inhibits TJ assembly. Activated Cdc42 can disrupt TJs [3Lin D. Edwards A.S. Fawcett J.P. Mbamalu G. Scott J.D. Pawson T. A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity.Nat. Cell Biol. 2000; 2: 540-547Crossref PubMed Scopus (47) Google Scholar, 4Joberty G. Petersen C. Gao L. Macara I.G. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42.Nat. Cell Biol. 2000; 2: 531-539Crossref PubMed Scopus (724) Google Scholar, 5Suzuki A. Yamanaka T. Hirose T. Manabe N. Mizuno K. Shimizu M. Akimoto K. Izumi Y. Ohnishi T. Ohno S. Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures.J. Cell Biol. 2001; 152: 1183-1196Crossref PubMed Scopus (371) Google Scholar], but neither a dominant-negative Cdc42 mutant nor the CRIB domain of γPAK (p21-activated kinase), which inhibits Cdc42 function, observably inhibit TJ formation. These results suggest that Cdc42 and Par6 negatively regulate TJ assembly in mammalian epithelial cells." @default.
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• W2000709179 date "2002-02-01" @default.
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• W2000709179 title "Assembly of Epithelial Tight Junctions Is Negatively Regulated by Par6" @default.
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• W2000709179 doi "https://doi.org/10.1016/s0960-9822(01)00663-7" @default.
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