Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization.
The molecular mechanisms of how primordial adherens junctions (AJs) evolve into spatially separated belt-like AJs and tight junctions (TJs) during epithelial polarization are not well understood. Previously, we reported the establishment of ZO-1/ZO-2-deficient cultured epithelial cells (1[ko]/2[kd] cells), which lacked TJs completely. In the present study, we found that the formation of belt-like AJs was significantly delayed in 1(ko)/2(kd) cells during epithelial polarization. The activation of Rac1 upon primordial AJ formation is severely impaired in 1(ko)/2(kd) cells. Our data indicate that ZO-1 plays crucial roles not only in TJ formation, but also in the conversion from "fibroblastic" AJs to belt-like "polarized epithelial" AJs through Rac1 activation. Furthermore, to examine whether ZO-1 itself mediate belt-like AJ and TJ formation, respectively, we performed a mutational analysis of ZO-1. The requirement for ZO-1 differs between belt-like AJ and TJ formation. We propose that ZO-1 is directly involved in the establishment of two distinct junctional domains, belt-like AJs and TJs, during epithelial polarization.
Ikenouchi
Junichi
J
Department of Cell Biology, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. ikenouti@mfour.med.kyoto-u.ac.jp
Umeda
Kazuaki
K
Tsukita
Sachiko
S
Furuse
Mikio
M
Tsukita
Shoichiro
S
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D022005:Adherens Junctions / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein
D008565:Membrane Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; C484602:Rac1 protein, mouse; C569043:Tjp1 protein, mouse; C569047:Tjp2 protein, mouse; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein