Mammalian LgI forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity

被引:287
作者
Yamanaka, T
Horikoshi, Y
Sugiyama, Y
Ishiyama, C
Suzuki, A
Hirose, T
Iwamatsu, A
Shinohara, A
Ohno, S
机构
[1] Yokohama City Univ, Sch Med, Dept Mol Biol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
[2] Kirin Brewery Co Ltd, Sect Prot Chem, Cent Labs Key Technol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
基金
日本学术振兴会;
关键词
D O I
10.1016/S0960-9822(03)00244-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Epithelial cells have apicobasal polarity and an asymmetric junctional complex that provides the bases for development and tissue maintenance. In both vertebrates and invertebrates, the evolutionarily conserved protein complex, PAR-6/aPKC/PAR-3, localizes to the subapical region and plays critical roles in the establishment of a junctional complex and cell polarity. In Drosophila, another set of proteins called tumor suppressors, such as LgI, which localize separately to the basolateral membrane domain but genetically interact with the subapical proteins, also contribute to the establishment of cell polarity. However, how physically separated proteins interact remains to be clarified. Results: We show that mammalian LgI competes for PAR-3 in forming an independent complex with PAR-6/ aPKC. During cell polarization, mLgI initially colocalizes with PAR-6/aPKC at the cell-cell contact region and is phosphorylated by aPKC, followed by segregation from apical PAR-6/aPKC to the basolateral membrane after cells are polarized. Overexpression studies establish that increased amounts of the mLgI/PAR-6/aPKC complex suppress the formation of epithelial junctions; this contrasts with the previous observation that the complex containing PAR-3 promotes it. Conclusions: These results indicate that PAR-6/aPKC selectively interacts with either mLgI or PAR-3 under the control of aPKC activity to regulate epithelial cell polarity.
引用
收藏
页码:734 / 743
页数:10
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