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First published online May 6, 2009

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Going apical with PAR-3

PAR-3 and the aPKC–PAR-6 complex – which are crucial proteins for establishing apicobasal polarity in epithelial cells – are thought to regulate the establishment of the apical domain, as well as the maturation of epithelial junctional structures such as tight junctions (TJs). The molecular mechanisms that underpin their roles have been unclear, although it has recently been shown that PAR-3 can regulate TJ development without interacting with aPKC–PAR-6. By contrast, Shigeo Ohno and colleagues (p. 1595) now show that apical-domain formation requires an interaction between PAR-3 and aPKC–PAR-6. The authors show that, in MDCK cells, knocking down PAR-3 inhibits exocytic delivery of apical proteins to the plasma membrane and eventually results in apical-domain mislocalisation; moreover, the cells fail to form normal cysts in 3D culture, and instead develop cysts that have multiple lumens. These defects can be rescued by wild-type PAR-3, but not by a PAR-3 mutant that cannot interact with aPKC. They next observe that, in depolarised MDCK cells, aPKC and PAR-6 (but not PAR-3) accumulate on apical vacuoles, and that these are targeted to PAR-3-containing primordial cell-cell contact sites as repolarisation progresses. Thus, the authors conclude, the formation of a PAR-3–aPKC–PAR-6 complex is necessary for apical-domain establishment.

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Related articles in JCS:

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

Yosuke Horikoshi, Atsushi Suzuki, Tomoyuki Yamanaka, Kazunori Sasaki, Keiko Mizuno, Hajime Sawada, Shigenobu Yonemura, and Shigeo Ohno
JCS 2009 122: 1595-1606. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?