Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions.
PAR-3 is a scaffold-like PDZ-containing protein that forms a complex with PAR-6 and atypical protein kinase C (PAR-3-atypical protein kinase C-PAR-6 complex) and contributes to the establishment of cell polarity in a wide variety of biological contexts. In mammalian epithelial cells, it localizes to tight junctions, the most apical end of epithelial cell-cell junctions, and contributes to the formation of functional tight junctions. However, the mechanism by which PAR-3 localizes to tight junctions and contributes to their formation remains to be clarified. Here we show that the N-terminal conserved region, CR1-(1-86), and the sequence 937-1,024 are required for its recruitment to the most apical side of the cell-cell contact region in epithelial Madin-Darby canine kidney cells. We also show that CR1 self-associates to form an oligomeric complex in vivo and in vitro. Further, overexpression of CR1 in Madin-Darby canine kidney cells disturbs the distribution of atypical protein kinase C and PAR-6 as well as PAR-3 and delays the formation of functional tight junctions. These results support the notion that the CR1-mediated self-association of the PAR-3-containing protein complex plays a role during the formation of functional tight junctions.
Mizuno
Keiko
K
Department of Molecular Biology, Yokohama City University School of Medicine, Fuku-ura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan.
Suzuki
Atsushi
A
Hirose
Tomonori
T
Kitamura
Koichi
K
Kutsuzawa
Koichi
K
Futaki
Masaaki
M
Amano
Yoshiko
Y
Ohno
Shigeo
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002450:Cell Communication / Q000502:physiology; D018797:Cell Cycle Proteins; D016764:Cell Polarity / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D019143:Evolution, Molecular; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D019108:Tight Junctions / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C115084:Pard3 protein, mouse; D011493:Protein Kinase C