RRC ID 4785
Author Suzuki A, Yamanaka T, Hirose T, Manabe N, Mizuno K, Shimizu M, Akimoto K, Izumi Y, Ohnishi T, Ohno S.
Title Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures.
Journal J Cell Biol
Abstract 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.
Volume 152(6)
Pages 1183-96
Published 2001-3-19
DOI 10.1083/jcb.152.6.1183
PMID 11257119
PMC PMC2199212
MeSH Actins / metabolism Adaptor Proteins, Signal Transducing Adenoviridae / genetics Adenoviridae / metabolism Animals Blotting, Western Cadherins / metabolism Caenorhabditis elegans Proteins* Calcium / metabolism Carrier Proteins* Cell Adhesion Molecules* Cell Cycle Proteins Cell Line Cell Polarity* Epithelial Cells / cytology Epithelial Cells / physiology* Epithelial Cells / ultrastructure Fluorescent Dyes / metabolism Gene Transfer Techniques Helminth Proteins / metabolism* Macromolecular Substances Membrane Lipids / metabolism Membrane Proteins / metabolism Microscopy, Fluorescence Occludin Phosphoproteins / metabolism Precipitin Tests Protein Kinase C / genetics Protein Kinase C / metabolism* Protein Serine-Threonine Kinases Proteins / genetics Proteins / metabolism Sodium-Potassium-Exchanging ATPase / metabolism Tight Junctions / metabolism* Zonula Occludens-1 Protein
IF 8.811
Times Cited 346
DNA material AxCANLacZ (RDB01749)