Adachi Makoto, Hamazaki Yoko, Kobayashi Yuka, Itoh Masahiko, Tsukita Sachiko, Furuse Mikio, Tsukita Shoichiro
Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Mol Cell Biol. 2009 May;29(9):2372-89. doi: 10.1128/MCB.01505-08. Epub 2009 Mar 2.
MUPP1 and Patj are both composed of an L27 domain and multiple PDZ domains (13 and 10 domains, respectively) and are localized to tight junctions (TJs) in epithelial cells. Although Patj is known to be responsible for the organization of TJs and epithelial polarity, characterization of MUPP1 is lacking. In this study, we found that MUPP1 and Patj share several binding partners, including JAM1, ZO-3, Pals1, Par6, and nectins (cell-cell adhesion molecules at adherens junctions). MUPP1 and Patj exhibited similar subcellular distributions, and the mechanisms with which they localize to TJs also appear to overlap. Despite these similarities, functional studies have revealed that Patj is indispensable for the establishment of TJs and epithelial polarization, whereas MUPP1 is not. Thus, although MUPP1 and Patj share several molecular properties, their functions are entirely different. We present evidence that the signaling mediated by Pals1, which has a higher affinity for Patj than for MUPP1 and is involved in the activation of the Par6-aPKC complex, is of principal importance for the function of Patj in epithelial cells.
MUPP1和Patj均由一个L27结构域和多个PDZ结构域组成(分别为13个和10个结构域),并定位于上皮细胞的紧密连接(TJ)处。尽管已知Patj负责紧密连接的组织和上皮极性,但MUPP1的特性尚缺乏研究。在本研究中,我们发现MUPP1和Patj共享多个结合伴侣,包括JAM1、ZO-3、Pals1、Par6和nectins(黏附连接中的细胞间黏附分子)。MUPP1和Patj表现出相似的亚细胞分布,并且它们定位于紧密连接的机制似乎也有重叠。尽管存在这些相似性,但功能研究表明,Patj对于紧密连接的建立和上皮极化是不可或缺的,而MUPP1并非如此。因此,尽管MUPP1和Patj具有若干分子特性,但它们的功能却完全不同。我们提供的证据表明,由Pals1介导的信号传导对Patj在上皮细胞中的功能至关重要,Pals1对Patj的亲和力高于对MUPP1的亲和力,并且参与Par6-aPKC复合物的激活。