Blankenship J Todd, Fuller Margaret T, Zallen Jennifer A
Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
J Cell Sci. 2007 Sep 1;120(Pt 17):3099-110. doi: 10.1242/jcs.004770. Epub 2007 Aug 14.
The polarized architecture of epithelial tissues involves a dynamic balance between apical and basolateral membrane domains. Here we show that epithelial polarity in the Drosophila embryo requires the exocyst complex subunit homolog Exo84. Exo84 activity is essential for the apical localization of the Crumbs transmembrane protein, a key determinant of epithelial apical identity. Adherens junction proteins become mislocalized at the cell surface in Exo84 mutants in a pattern characteristic of defects in apical, but not basolateral, components. Loss of Crumbs from the cell surface precedes the disruption of Bazooka and Armadillo localization in Exo84 mutants. Moreover, Exo84 mutants display defects in apical cuticle secretion that are similar to crumbs mutants and are suppressed by a reduction in the basolateral proteins Dlg and Lgl. In Exo84 mutants at advanced stages of epithelial degeneration, apical and adherens junction proteins accumulate in an expanded recycling endosome compartment. These results suggest that epithelial polarity in the Drosophila embryo is actively maintained by exocyst-dependent apical localization of the Crumbs transmembrane protein.
上皮组织的极化结构涉及顶端和基底外侧膜结构域之间的动态平衡。我们在此表明,果蝇胚胎中的上皮极性需要外泌体复合物亚基同源物Exo84。Exo84的活性对于跨膜蛋白Crumb(上皮顶端身份的关键决定因素)的顶端定位至关重要。在Exo84突变体中,黏着连接蛋白在细胞表面发生错误定位,其模式是顶端而非基底外侧成分缺陷的特征。在Exo84突变体中,细胞表面Crumb的缺失先于Bazooka和Armadillo定位的破坏。此外,Exo84突变体在顶端角质层分泌方面表现出缺陷,这与crumbs突变体相似,并被基底外侧蛋白Dlg和Lgl的减少所抑制。在上皮退化晚期的Exo84突变体中,顶端和黏着连接蛋白积聚在一个扩大的再循环内体区室中。这些结果表明,果蝇胚胎中的上皮极性是通过外泌体依赖的Crumb跨膜蛋白顶端定位来积极维持的。