1. Interaction between PAR-3 and the aPKC—PAR-6 complex is indispensable for apical domain development of epithelial cells.
- Author
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Horikoshi, Yosuke, Suzuki, Atsushi, Tomoyuki Yamanaka, Sasaki, Kazunori, Mizuno, Keiko, Sawada, Hajime, Yonemura, Shigenobu, and Ohno, Shigeo
- Subjects
PROTEIN kinase C ,EPITHELIAL cells ,CELL membranes ,EPITHELIUM ,CELL polarity ,MOLECULAR biology - Abstract
The evolutionarily conserved polarity proteins PAR-3, atypical protein kinase C (aPKC) and PAR-6 critically regulate the apical membrane development required for epithelial organ development. However, the molecular mechanisms underlying their roles remain to be clarified. We demonstrate that PAR-3 knockdown in MDCK cells retards apical protein delivery to the plasma membrane, and eventually leads to mislocalized apical domain formation at intercellular regions in both two-dimensional and three-dimensional culture systems. The defects in PAR-3 knockdown cells are efficiently rescued by wild-type PAR-3, but not by a point mutant (S827/829A) that lacks the ability to interact with aPKC, indicating that formation of the PAR-3-aPKC-PAR-6 complex is essential for apical membrane development. This is in sharp contrast with tight junction maturation, which does not necessarily depend on the aPKC-PAR-3 interaction, and indicates that the two fundamental processes essential for epithelial polarity are differentially regulated by these polarity proteins. Importantly, highly depolarized cells accumulate aPKC and PAR-6, but not PAR-3, on apical protein-containing vacuoles, which become targeted to PAR-3-positive primordial cell-cell contact sites during the initial stage of the repolarization process. Therefore, formation of the PAR-3-aPKC-PAR-6 complex might be required for targeting of not only the aPKC-PAR-6 complex but also of apical protein carrier vesicles to primordial junction structures. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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