Establishment of cell polarity by afadin during the formation of embryoid bodies.
Afadin directly links nectin, an immunoglobulin-like cell-cell adhesion molecule, to actin filaments (F-actin) at adherens junctions (AJs). The nectin-afadin complex is important for the formation of not only AJs but also tight junctions (TJs) in epithelial cells. Studies using afadin-knockout mice have revealed that afadin is indispensable for embryonic development by organizing the formation of cell-cell junctions. However, the molecular mechanism of cell-cell junction disorganization during embryonic development in afadin-knockout mice is poorly understood. To address this, we took advantage of embryoid bodies (EBs) as a model system. The formation of cell-cell junctions including AJs and TJs was impaired in afadin-null EBs. The proper accumulation of the Par complex and the activation of Cdc42 and atypical PKC (aPKC), which are crucial for the formation of cell polarity, were also inhibited by knockout of afadin. In addition, the disruption of afadin caused the abnormal deposition of laminin and the dislocalization of its receptors integrin alpha(6) and integrin beta(1). These results indicate that afadin organizes the formation of cell-cell junctions by regulating cell polarization in early embryonic development.
Komura
Hitomi
H
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan.
Ogita
Hisakazu
H
Ikeda
Wataru
W
Mizoguchi
Akira
A
Miyoshi
Jun
J
Takai
Yoshimi
Y
D022005:Adherens Junctions / Q000502:physiology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D039423:Integrin alpha1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D000075983:Nectins; D019108:Tight Junctions / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D015815:Cell Adhesion Molecules; D039423:Integrin alpha1; D019012:Integrin beta1; D007797:Laminin; D008840:Microfilament Proteins; D000075983:Nectins; C108835:afadin; D020764:cdc42 GTP-Binding Protein