Cooperative roles of Par-3 and afadin in the formation of adherens and tight junctions.
Par-3 is a cell-polarity protein that regulates the formation of tight junctions (TJs) in epithelial cells, where claudin is a major cell-cell adhesion molecule (CAM). TJs are formed at the apical side of adherens junctions (AJs), where E-cadherin and nectin are major CAMs. We have revealed that nectin first forms cell-cell adhesions, and then recruits cadherin to nectin-based cell-cell adhesion sites to form AJs and subsequently recruits claudin to the apical side of AJs to form TJs. The cytoplasmic tail of nectin binds afadin and Par-3. Afadin regulates the formation of AJs and TJs cooperatively with nectin. Here, we studied the role of Par-3 in the formation of these junctions by using Par-3-knockdown MDCK cells. Par-3 was necessary for the formation of AJs and TJs but was not necessary for nectin-based cell-cell adhesion. Par-3 promoted the association of afadin with nectin, whereas afadin was not necessary for the association of Par-3 with nectin. However, the association of afadin with nectin alone was not sufficient for the formation of AJs or TJs, and Par-3 and afadin cooperatively regulated it. We describe here these novel roles of Par-3 in the formation of junctional complexes.
Ooshio
Takako
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
Fujita
Naoyuki
N
Yamada
Akio
A
Sato
Tatsuhiro
T
Kitagawa
Yuichi
Y
Okamoto
Ryoko
R
Nakata
Shinsuke
S
Miki
Ayaka
A
Irie
Kenji
K
Takai
Yoshimi
Y
D022005:Adherens Junctions / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D015820:Cadherins / Q000302:isolation & purification / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000302:isolation & purification / Q000378:metabolism; D062445:Claudin-1; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000075983:Nectins; D019108:Tight Junctions / Q000378:metabolism* / Q000502:physiology; D051178:alpha Catenin / Q000302:isolation & purification / Q000378:metabolism; D051176:beta Catenin / Q000302:isolation & purification / Q000378:metabolism
D015820:Cadherins; D015815:Cell Adhesion Molecules; D062445:Claudin-1; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000075983:Nectins; C108835:afadin; D051178:alpha Catenin; D051176:beta Catenin