Intracellular polarity protein PAR-1 regulates extracellular laminin assembly by regulating the dystroglycan complex
Intracellular polarity protein PAR-1 regulates extracellular laminin assembly by regulating the dystroglycan complex
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DOI：
10.1111/j.1365-2443.2009.01315.x
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发表时间：
2009-07-01
期刊：
影响因子：
2.1
通讯作者：
Ohno, Shigeo
中科院分区：
文献类型：
--
作者：
Masuda-Hirata, Maki;Suzuki, Atsushi;Ohno, Shigeo
细胞极性取决于外部空间线索和内在极性蛋白，包括PAR-aPKC蛋白。在哺乳动物上皮细胞中，细胞间接触提供了激活aPKC-PAR-3-PAR-6复合体的空间线索，以建立初始细胞不对称的标志。PAR-1是aPKC-PAR-3-PAR-6复合物的下游靶点，介导根尖和基底外侧膜结构域的进一步发育。然而，PAR-aPKC蛋白与细胞外基质（ECM）提供的其他外部空间线索之间的关系尚不清楚。在这里，我们发现PAR-1与层粘连蛋白受体共定位，并且是上皮细胞基表面细胞外层粘连蛋白组装所必需的。此外，PAR-1还调节三聚糖酐（DG）复合物的基底外侧定位，DG复合物是基膜形成所必需的层粘连蛋白受体之一。我们还表明PAR-1与DG复合物相互作用，并且是形成功能性DG复合物所必需的。这些结果揭示了细胞内极性蛋白调节上皮细胞极性和组织形态发生所需的ECM组织的一种新的由内向外途径的存在。
Cell polarity depends on extrinsic spatial cues and intrinsic polarity proteins including PAR-aPKC proteins. In mammalian epithelial cells, cell-cell contacts provide spatial cues that activate the aPKC-PAR-3-PAR-6 complex to establish the landmark of the initial cellular asymmetry. PAR-1, a downstream target of the aPKC-PAR-3-PAR-6 complex, mediates further development of the apical and basolateral membrane domains. However, the relationships between the PAR-aPKC proteins and other extrinsic spatial cues provided by the extracellular matrix (ECM) remain unclear. Here, we show that PAR-1 colocalizes with laminin receptors and is required for the assembly of extracellular laminin on the basal surface of epithelial cells. Furthermore, PAR-1 regulates the basolateral localization of the dystroglycan (DG) complex, one of the laminin receptors essential for basement membrane formation. We also show that PAR-1 interacts with the DG complex and is required for the formation of a functional DG complex. These results reveal the presence of a novel inside-out pathway in which an intracellular polarity protein regulates the ECM organization required for epithelial cell polarity and tissue morphogenesis.