Navarro Caryn, Puthalakath Hamsa, Adams Jerry M, Strasser Andreas, Lehmann Ruth
Developmental Genetics Program and The Department of Cell Biology, The Skirball Institute and Howard Hughes Medical Institute, NYU School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Nat Cell Biol. 2004 May;6(5):427-35. doi: 10.1038/ncb1122. Epub 2004 Apr 11.
In many cell types polarized transport directs the movement of mRNAs and proteins from their site of synthesis to their site of action, thus conferring cell polarity. The cytoplasmic dynein microtubule motor complex is involved in this process. In Drosophila melanogaster, the Egalitarian (Egl) and Bicaudal-D (BicD) proteins are also essential for the transport of macromolecules to the oocyte and to the apical surface of the blastoderm embryo. Hence, Egl and BicD, which have been shown to associate, may be part of a conserved core localization machinery in Drosophila, although a direct association between these molecules and the dynein motor complex has not been shown. Here we report that Egl interacts directly with Drosophila dynein light chain (Dlc), a microtubule motor component, through an Egl domain distinct from that which binds BicD. We propose that the Egl-BicD complex is loaded through Dlc onto the dynein motor complex thereby facilitating transport of cargo. Consistent with this model, point mutations that specifically disrupt Egl-Dlc association also disrupt microtubule-dependant trafficking both to and within the oocyte, resulting in a loss of oocyte fate maintenance and polarity. Our data provide a direct link between a molecule necessary for oocyte specification and the microtubule motor complex, and supports the hypothesis that microtubule-mediated transport is important for preserving oocyte fate.
在许多细胞类型中，极性运输引导信使核糖核酸（mRNA）和蛋白质从其合成位点移动到作用位点，从而赋予细胞极性。胞质动力蛋白微管运动复合体参与了这一过程。在黑腹果蝇中，平等蛋白（Egl）和双尾-D蛋白（BicD）对于将大分子运输到卵母细胞和胚盘胚胎的顶端表面也至关重要。因此，已证明相互关联的Egl和BicD可能是果蝇中保守的核心定位机制的一部分，尽管尚未证明这些分子与动力蛋白运动复合体之间存在直接关联。在此我们报告，Egl通过一个不同于与BicD结合的结构域，直接与果蝇动力蛋白轻链（Dlc，一种微管运动成分）相互作用。我们提出，Egl-BicD复合体通过Dlc加载到动力蛋白运动复合体上，从而促进货物运输。与该模型一致，特异性破坏Egl-Dlc关联的点突变也会破坏卵母细胞内外依赖微管的运输，导致卵母细胞命运维持和极性丧失。我们的数据提供了卵母细胞特化所需分子与微管运动复合体之间的直接联系，并支持微管介导的运输对维持卵母细胞命运很重要这一假说。
