Perlecan and Dystroglycan act at the basal side of the Drosophila follicular epithelium to maintain epithelial organization
Perlecan and Dystroglycan act at the basal side of the Drosophila follicular epithelium to maintain epithelial organization
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DOI：
10.1242/dev.02549
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发表时间：
2006-10-01
期刊：
影响因子：
4.6
通讯作者：
Baumgartner, Stefan
中科院分区：
文献类型：
--
作者：
Schneider, Martina;Khalil, Ashraf A.;Baumgartner, Stefan
糖代谢障碍（Dg）是一种广泛表达的细胞外基质（ECM）受体，是肌肉活力、突触发生、基底膜形成和上皮发育所必需的。作为肌营养不良蛋白相关糖蛋白复合物的一个组成部分，Dg在连接ECM和细胞骨架中起着核心作用。骨骼肌中这种联系的破坏会导致各种类型的肌肉萎缩症。在上皮细胞中，Dg表达的减少与癌细胞侵袭性的增加有关。我们之前已经证明Dg是果蝇上皮细胞极性所必需的，但是这种极化活性的机制和上下游成分在很大程度上是未知的。使用果蝇滤泡细胞上皮（FCE）作为模型系统，我们发现ECM分子Perlecan （Pcan）是维持上皮细胞极性所必需的。缺少p的卵泡细胞会产生与Dg突变细胞相似的极性缺陷。此外，Dg依赖于Pcan而不是层粘连蛋白A来定位基底细胞膜，并且这两种蛋白在体外结合。有趣的是，在FCE中与Pcan相互作用的Dg形式缺乏粘蛋白样结构域，这被认为是Dg配体结合活性所必需的。最后，我们描述了Dg如何促进基膜结构域分化的两个例子：(1)通过募集/锚定细胞质蛋白肌营养不良蛋白；(2)通过排除跨膜蛋白Neurexin。我们认为Pcan和Dg在上皮基底侧的相互作用促进了基底膜的分化，并且是维持FCE中细胞极性所必需的。
Dystroglycan (Dg) is a widely expressed extracellular matrix (ECM) receptor required for muscle viability, synaptogenesis, basement-membrane formation and epithelial development. As an integral component of the Dystrophin-associated glycoprotein complex, Dg plays a central role in linking the ECM and the cytoskeleton. Disruption of this linkage in skeletal muscle leads to various types of muscular dystrophies. In epithelial cells, reduced expression of Dg is associated with increased invasiveness of cancer cells. We have previously shown that Dg is required for epithelial cell polarity in Drosophila, but the mechanisms of this polarizing activity and upstream/downstream components are largely unknown. Using the Drosophila follicle-cell epithelium (FCE) as a model system, we show that the ECM molecule Perlecan (Pcan) is required for maintenance of epithelial-cell polarity. Follicle cells that lack Pcan develop polarity defects similar to those of Dg mutant cells. Furthermore, Dg depends on Pcan but not on Laminin A for its localization in the basal-cell membrane, and the two proteins bind in vitro. Interestingly, the Dg form that interacts with Pcan in the FCE lacks the mucin-like domain, which is thought to be essential for Dg ligand binding activity. Finally, we describe two examples of how Dg promotes the differentiation of the basal membrane domain: (1) by recruiting/anchoring the cytoplasmic protein Dystrophin; and (2) by excluding the transmembrane protein Neurexin. We suggest that the interaction of Pcan and Dg at the basal side of the epithelium promotes basal membrane differentiation and is required for maintenance of cell polarity in the FCE.