Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity.
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 Lgl, 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 Lgl competes for PAR-3 in forming an independent complex with PAR-6/aPKC. During cell polarization, mLgl 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 mLgl/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 mLgl or PAR-3 under the control of aPKC activity to regulate epithelial cell polarity.
Yamanaka
Tomoyuki
T
Department of Molecular Biology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Japan.
Horikoshi
Yosuke
Y
Sugiyama
Yuki
Y
Ishiyama
Chikako
C
Suzuki
Atsushi
A
Hirose
Tomonori
T
Iwamatsu
Akihiro
A
Shinohara
Azusa
A
Ohno
Shigeo
S
D000257:Adenoviridae Infections / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001681:Biological Assay; D015153:Blotting, Western; D016764:Cell Polarity / Q000502:physiology*; D002999:Clone Cells / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D000906:Antibodies; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; C082939:Llgl1 protein, mouse; D011506:Proteins; D025521:Tumor Suppressor Proteins; C115015:PKC-3 protein; D011493:Protein Kinase C