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Published online 19 March 2001. doi:10.1083/jcb.152.6.1183
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© The Rockefeller University Press, 0021-9525/2001//1183 $5.00
The Journal of Cell Biology, Volume 152, Number 6, , 2001 1183-1196

Original Article

Atypical Protein Kinase C Is Involved in the Evolutionarily Conserved Par Protein Complex and Plays a Critical Role in Establishing Epithelia-Specific Junctional Structures



Atsushi Suzukia, Tomoyuki Yamanakaa, Tomonori Hirosea, Naoyuki Manabea, Keiko Mizunoa, Miki Shimizua, Kazunori Akimotoa, Yasushi Izumia, Tetsuo Ohnishia, and Shigeo Ohnoa

a Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Department of Molecular Biology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama 236, Japan.81-045-785-414081-045-787-2596

ohnos{at}med.yokohama-cu.ac.jp

We have previously shown that during early Caenorhabditis elegans embryogenesis PKC-3, a C. elegans atypical PKC (aPKC), plays critical roles in the establishment of cell polarity required for subsequent asymmetric cleavage by interacting with PAR-3 [Tabuse, Y., Y. Izumi, F. Piano, K.J. Kemphues, J. Miwa, and S. Ohno. 1998. Development (Camb.). 125:3607–3614]. Together with the fact that aPKC and a mammalian PAR-3 homologue, aPKC-specific interacting protein (ASIP), colocalize at the tight junctions of polarized epithelial cells (Izumi, Y., H. Hirose, Y. Tamai, S.-I. Hirai, Y. Nagashima, T. Fujimoto, Y. Tabuse, K.J. Kemphues, and S. Ohno. 1998. J. Cell Biol. 143:95–106), this suggests a ubiquitous role for aPKC in establishing cell polarity in multicellular organisms. Here, we show that the overexpression of a dominant-negative mutant of aPKC (aPKCkn) in MDCK II cells causes mislocalization of ASIP/PAR-3. Immunocytochemical analyses, as well as measurements of paracellular diffusion of ions or nonionic solutes, demonstrate that the biogenesis of the tight junction structure itself is severely affected in aPKCkn-expressing cells. Furthermore, these cells show increased interdomain diffusion of fluorescent lipid and disruption of the polarized distribution of Na+,K+-ATPase, suggesting that epithelial cell surface polarity is severely impaired in these cells. On the other hand, we also found that aPKC associates not only with ASIP/PAR-3, but also with a mammalian homologue of C. elegans PAR-6 (mPAR-6), and thereby mediates the formation of an aPKC-ASIP/PAR-3–PAR-6 ternary complex that localizes to the apical junctional region of MDCK cells. These results indicate that aPKC is involved in the evolutionarily conserved PAR protein complex, and plays critical roles in the development of the junctional structures and apico-basal polarization of mammalian epithelial cells.

Key Words: atypical PKC • tight junction • epithelial cell polarity • PAR-3 • PAR-6

© 2001 The Rockefeller University Press

The online version of this article contains supplemental material.

Drs. Suzuki and Yamanaka contributed equally to this work and should be considered co-first authors.

Dr. Izumi's present address is Department of Developmental Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.

Abbreviations used in this paper: AJ, adherent junction; aPKC, atypical PKC; ASIP, aPKC-specific interacting protein; LC, low Ca2+; NC, normal Ca2+; NKA, Na+, K+-ATPase; TER, transepithelial electrical resistance; TJ, tight junction.


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