Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity.
The basolateral tumor suppressor protein Lgl is important for the regulation of epithelial cell polarity and tissue morphology. Recent studies have shown a physical and functional interaction of Lgl with another polarity-regulating protein machinery, the apical PAR-3-aPKC-PAR-6 complex, in epithelial cells. However, the mechanism of Lgl-mediated regulation of epithelial cell polarity remains obscure. By an siRNA method, we here show that endogenous Lgl is required for the disassembly of apical membrane domains in depolarizing MDCK cells induced by Ca2+ depletion. Importantly, this Lgl function is mediated by the suppression of the apical PAR-3-aPKC-PAR-6 complex activity. Analysis using 2D- or 3D-cultured cells in collagen gel suggests the importance of this suppressive regulation of Lgl on the collagen-mediated re-establishment of apical membrane domains and lumen formation. These results indicate that basolateral Lgl plays a crucial role in the disassembly of apical membrane domains to induce the orientation of apical membrane polarity, which is mediated by the suppression of apical PAR-3-aPKC-PAR-6 complex activity.
Yamanaka
Tomoyuki
T
Department of Molecular Biology, Yokohama City University, Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
Horikoshi
Yosuke
Y
Izumi
Natsuko
N
Suzuki
Atsushi
A
Mizuno
Keiko
K
Ohno
Shigeo
S
D000818:Animals; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D003094:Collagen; D003598:Cytoskeletal Proteins; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D018179:Receptors, Thrombin / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; C082939:Llgl1 protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D018179:Receptors, Thrombin; D025521:Tumor Suppressor Proteins; C105295:protease-activated receptor 3; D003094:Collagen; D011493:Protein Kinase C