Mammalian LgI forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity
Mammalian LgI forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity
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DOI：
10.1016/s0960-9822(03)00244-6
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发表时间：
2003-04-29
期刊：
影响因子：
9.2
通讯作者：
Ohno, S
中科院分区：
文献类型：
--
作者：
Yamanaka, T;Horikoshi, Y;Ohno, S
背景资料：上皮细胞具有顶基极性和不对称的连接复合体，为发育和组织维持提供基础。在脊椎动物和无脊椎动物中，进化上保守的蛋白质复合物PAR-6/aPKC/PAR-3定位于根尖下区域，并在连接复合物和细胞极性的建立中起关键作用。在果蝇中，另一组称为肿瘤抑制因子的蛋白质，如LgI，其分别定位于基底外侧膜结构域，但与亚顶端蛋白质发生遗传相互作用，也有助于细胞极性的建立。然而，如何物理分离的蛋白质相互作用仍有待澄清。结果：我们表明，哺乳动物的LgI竞争PAR-3在形成一个独立的复合物与PAR-6/ aPKC。在细胞极化过程中，mLgI最初与PAR-6/aPKC共定位于细胞-细胞接触区，并被aPKC磷酸化，然后在细胞极化后从顶端PAR-6/aPKC分离到基底外侧膜。过表达的研究建立，增加量的mLgI/PAR-6/aPKC复合物抑制上皮连接的形成，这与以前的观察，复合物含有PAR-3促进它。结论：这些结果表明，PAR-6/aPKC选择性地相互作用与mLgI或PAR-3下的aPKC活性的控制，以调节上皮细胞极性。
Background: Epithelial cells have apicobasal polarity and an asymmetric junctional complex that provides the bases for development and tissue maintenance. In both vertebrates and invertebrates, the evolutionarily conserved protein complex, PAR-6/aPKC/PAR-3, localizes to the subapical region and plays critical roles in the establishment of a junctional complex and cell polarity. In Drosophila, another set of proteins called tumor suppressors, such as LgI, which localize separately to the basolateral membrane domain but genetically interact with the subapical proteins, also contribute to the establishment of cell polarity. However, how physically separated proteins interact remains to be clarified.Results: We show that mammalian LgI competes for PAR-3 in forming an independent complex with PAR-6/ aPKC. During cell polarization, mLgI initially colocalizes with PAR-6/aPKC at the cell-cell contact region and is phosphorylated by aPKC, followed by segregation from apical PAR-6/aPKC to the basolateral membrane after cells are polarized. Overexpression studies establish that increased amounts of the mLgI/PAR-6/aPKC complex suppress the formation of epithelial junctions; this contrasts with the previous observation that the complex containing PAR-3 promotes it.Conclusions: These results indicate that PAR-6/aPKC selectively interacts with either mLgI or PAR-3 under the control of aPKC activity to regulate epithelial cell polarity.