The keratin-binding protein Albatross regulates polarization of epithelial cells.
The keratin intermediate filament network is abundant in epithelial cells, but its function in the establishment and maintenance of cell polarity is unclear. Here, we show that Albatross complexes with Par3 to regulate formation of the apical junctional complex (AJC) and maintain lateral membrane identity. In nonpolarized epithelial cells, Albatross localizes with keratin filaments, whereas in polarized epithelial cells, Albatross is primarily localized in the vicinity of the AJC. Knockdown of Albatross in polarized cells causes a disappearance of key components of the AJC at cell-cell borders and keratin filament reorganization. Lateral proteins E-cadherin and desmoglein 2 were mislocalized even on the apical side. Although Albatross promotes localization of Par3 to the AJC, Par3 and ezrin are still retained at the apical surface in Albatross knockdown cells, which retain intact microvilli. Analysis of keratin-deficient epithelial cells revealed that keratins are required to stabilize the Albatross protein, thus promoting the formation of AJC. We propose that keratins and the keratin-binding protein Albatross are important for epithelial cell polarization.
Sugimoto
Masahiko
M
Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-8681, Japan.
Inoko
Akihito
A
Shiromizu
Takashi
T
Nakayama
Masanori
M
Zou
Peng
P
Yonemura
Shigenobu
S
Hayashi
Yuko
Y
Izawa
Ichiro
I
Sasoh
Mikio
M
Uji
Yukitaka
Y
Kaibuchi
Kozo
K
Kiyono
Tohru
T
Inagaki
Masaki
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000825:Animal Structures / Q000378:metabolism; D000818:Animals; D001648:Bile Canaliculi / Q000378:metabolism; D001665:Binding Sites; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002449:Cell Aggregation / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051301:Desmoglein 2 / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D053538:Keratin-18 / Q000378:metabolism; D053533:Keratin-8 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D062826:Zonula Occludens-1 Protein; D000099149:Ezrin
D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D051301:Desmoglein 2; D053538:Keratin-18; D053533:Keratin-8; D008565:Membrane Proteins; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; D000099149:Ezrin; C495314:DSG2 protein, human; C095245:FBF1 protein, human; C533180:Fbf1 protein, mouse; C488421:KRT18 protein, human; C426203:KRT8 protein, human; C509689:PARD3 protein, human; C115084:Pard3 protein, mouse; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse