Lano, a novel LAP protein directly connected to MAGUK proteins in epithelial cells
Lano, a novel LAP protein directly connected to MAGUK proteins in epithelial cells
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DOI：
10.1074/jbc.c100330200
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发表时间：
2001-08-24
影响因子：
4.8
通讯作者：
Borg, JP
中科院分区：
文献类型：
--
作者：
Saito, H;Santoni, MJ;Borg, JP
蛋白质网络不对称地分布于基底侧和顶端上皮膜，维持上皮组织的细胞极性和稳态。在非脊椎动物中的遗传学研究将两个基底外侧蛋白家族MAGUK（膜相关和鸟苷酸激酶）和MAGUK（富含亮氨酸的重复序列和PDZ）蛋白分配到对上皮结构至关重要的共同途径，并充当恶性肿瘤的看门人。在哺乳动物中，已经描述了三种densin蛋白，Densin-180，Erbin和hScribble。在这里，我们确定了一种名为拉诺（Lano）的蛋白质（无PDZ），仅存在于脊椎动物中，并与PDZ蛋白质具有很强的同一性。尽管缺乏PDZ结构域，但Lano以与Erbin和hScribble相似的方式位于上皮细胞的基底外侧。使用体外和体内实验，我们证明了Lano直接与MAGUK蛋白的PDZ结构域相互作用，包括上皮细胞中的hDLG（人椎间盘大）。第二池拉诺是复杂的埃尔宾。这些LAP-MAGUK蛋白复合物共存于上皮细胞的基底外侧。我们提供的证据表明，MAGUK和MAGUK蛋白之间的直接相互作用，我们提出，各种LAP-MAGUK网络靶向的基底侧的上皮细胞参与上皮组织和肿瘤生长的稳态。
Protein networks asymetrically distributed to basolateral and apical epithelial membranes maintain cell polarity and homeostasis of epithelial tissues. Genetic studies in non-vertebrates assigned two families of basolateral proteins, MAGUK (Membrane-associated and guanylate kinase) and LAP (leucine-rich repeats and PDZ) proteins, to a common pathway crucial for the epithelial architecture and acting as a gatekeeper to malignancy. In mammals, three LAP proteins have been described, Densin-180, Erbin, and hScribble. Here, we identify a protein called Lano (LAP and no PDZ) only present in vertebrates and presenting strong identities with LAP proteins. Despite the lack of PDZ domain, Lano is located at the basolateral side of epithelial cells in a similar manner to Erbin and hScribble. Using in vitro and in vivo experiments, we demonstrate that Lano directly interacts with the PDZ domains of MAGUK proteins, including hDLG (human disc large), in epithelial cells. A second pool of Lano is complexed to Erbin. These LAP-MAGUK protein complexes coexist at the basolateral side of epithelial cells. We provide evidence for a direct interaction between LAP and MAGUK proteins, and we propose that various LAP-MAGUK networks targeted to the basolateral side of epithelial cells participate to homeostasis of epithelial tissues and tumor growth.