Requirement of PDZ-containing proteins for cell cycle regulation and differentiation in the mouse lens epithelium
Requirement of PDZ-containing proteins for cell cycle regulation and differentiation in the mouse lens epithelium
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DOI：
10.1128/mcb.23.24.8970-8981.2003
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发表时间：
2003-12-01
影响因子：
5.3
通讯作者：
Griep, AE
中科院分区：
文献类型：
--
作者：
Nguyen, MM;Nguyen, ML;Griep, AE
含有PDZ结构域的蛋白质如Dig和Scrib的作用在果蝇中已经有了很好的描述;然而，它们对哺乳动物发育的需求却知之甚少。在这里，我们表明，Dlg，Scrib，MAGI 1，MAGI 3和MPDZ在小鼠眼透镜中表达。我们证明，在晶状体上皮细胞中观察到的细胞粘附和分化的增殖和缺陷的增加，表达E6，一种病毒癌蛋白，可以结合到几个PDZ蛋白，包括人类同源物的Dig和Scrib，是依赖于E6的能力，通过其PDZ结构域结合这些蛋白。对来自携带Dlg插入突变（dlg（gt））的小鼠的晶状体的分析显示增殖增加和透镜的空间不适当区域的增殖，这是与表达E6的晶状体的表型相似的表型。这项研究的结果表明，多种PDZ结构域的蛋白质，包括挖掘和Scrib，可能需要维持正常模式的生长和分化的透镜。此外，果蝇dlg突变体，dlg（gt）小鼠的晶状体和E6转基因小鼠的晶状体之间的表型相似性表明，Dlg可能在调节跨物种上皮细胞生长和分化中具有保守的功能。
The roles of PDZ domain-containing proteins such as Dig and Scrib have been well described for Drosophila; however, their requirement for mammalian development is poorly understood. Here we show that Dlg, Scrib, MAGI1, MAGI3, and MPDZ are expressed in the mouse ocular lens. We demonstrate that the increase in proliferation and defects in cellular adhesion and differentiation observed in epithelia of lenses that express E6, a viral oncoprotein that can bind to several PDZ proteins, including the human homologs of Dig and Scrib, is dependent on E6's ability to bind these proteins via their PDZ domains. Analyses of lenses from mice carrying an insertional mutation in Dlg (dlg(gt)) show increased proliferation and proliferation in spatially inappropriate regions of the lens, a phenotype similar to that of lenses expressing E6. The results from this study indicate that multiple PDZ domain-containing proteins, including Dig and Scrib, may be required for maintaining the normal pattern of growth and differentiation in the lens. Furthermore, the phenotypic similarities among the Drosophila dlg mutant, the lenses of dlg(gt) mice, and the lenses of E6 transgenic mice, suggest that Dlg may have a conserved function in regulating epithelial cell growth and differentiation across species.