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First published online 28 April 2009
doi: 10.1242/jcs.043174

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Interaction between PAR-3 and the aPKC–PAR-6 complex is indispensable for apical domain development of epithelial cells

Yosuke Horikoshi^1,*, Atsushi Suzuki¹, Tomoyuki Yamanaka^1,, Kazunori Sasaki¹, Keiko Mizuno¹, Hajime Sawada², Shigenobu Yonemura³ and Shigeo Ohno^1,

¹ Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan
² Department of Histology and Cell Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan
³ Electron Microscope Laboratory, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan

Author for correspondence (e-mail: ohnos{at}med.yokohama-cu.ac.jp)

Accepted 10 February 2009

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.

Key words: PAR, aPKC, Epithelial cells, Polarity, Apical domain

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