Sugimoto Masahiko, Inoko Akihito, Shiromizu Takashi, Nakayama Masanori, Zou Peng, Yonemura Shigenobu, Hayashi Yuko, Izawa Ichiro, Sasoh Mikio, Uji Yukitaka, Kaibuchi Kozo, Kiyono Tohru, Inagaki Masaki
Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464-8681, Japan.
J Cell Biol. 2008 Oct 6;183(1):19-28. doi: 10.1083/jcb.200803133.
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.
角蛋白中间丝网络在上皮细胞中含量丰富，但其在细胞极性建立和维持中的功能尚不清楚。在此，我们表明信天翁与Par3形成复合物，以调节顶端连接复合体（AJC）的形成并维持侧膜特性。在非极化上皮细胞中，信天翁与角蛋白丝共定位，而在极化上皮细胞中，信天翁主要定位于AJC附近。在极化细胞中敲低信天翁会导致AJC的关键成分在细胞-细胞边界处消失以及角蛋白丝重新组织。侧向蛋白E-钙黏蛋白和桥粒芯糖蛋白2即使在顶端侧也发生了错误定位。尽管信天翁促进Par3定位到AJC，但在敲低信天翁的细胞中，Par3和埃兹蛋白仍保留在顶端表面，这些细胞保留完整的微绒毛。对角蛋白缺陷上皮细胞的分析表明，角蛋白是稳定信天翁蛋白所必需的，从而促进AJC的形成。我们提出角蛋白和角蛋白结合蛋白信天翁对上皮细胞极化很重要。
