Vendra Georgia, Hamilton Russell S, Davis Ilan
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
RNA. 2007 Nov;13(11):1860-7. doi: 10.1261/rna.509007. Epub 2007 Sep 27.
Motor dependent transport of mRNA is a key mechanism in axis specification during development. Apical transport and anchoring of wingless and pair-rule transcripts in the Drosophila syncytial blastoderm embryo is mediated by cytoplasmic Dynein, the major minus end directed microtubule dependent molecular motor. Here, we show that, despite apical transport of mRNA being highly directional, mRNA particles often pause and move backward toward the plus ends of microtubules. We suggest that this retrograde movement helps overcome cellular obstructions. We show that the plus end movement of apical mRNA is independent of the major plus end microtubule motors Kinesin-1 and Kinesin-2. In contrast, Dynactin, a Dynein processivity factor, is required to suppress retrograde mRNA movements, as well as for efficient minus end motility. We propose that Dynein itself, rather than the activity of a plus end motor, is responsible for the plus end movements of the mRNA and that Dynactin is involved in preventing short reverse movements of the Dynein motor, known to occur in vitro.
mRNA的运动依赖性运输是发育过程中轴特化的关键机制。在果蝇合胞体胚盘胚胎中,无翅基因和成对规则转录本的顶端运输与锚定由胞质动力蛋白介导,胞质动力蛋白是主要的向微管负端移动的分子马达。在这里,我们表明,尽管mRNA的顶端运输具有高度方向性,但mRNA颗粒经常会暂停并向微管正端反向移动。我们认为这种逆行运动有助于克服细胞障碍。我们表明,顶端mRNA的正端移动独立于主要的微管正端马达驱动蛋白-1和驱动蛋白-2。相比之下,动力蛋白激活蛋白复合体,一种动力蛋白持续因子,对于抑制mRNA的逆行运动以及高效的向负端移动是必需的。我们提出,动力蛋白本身而非正端马达的活性,负责mRNA的正端移动,并且动力蛋白激活蛋白复合体参与防止动力蛋白马达已知在体外发生的短距离反向移动。