Januschke Jens, Gervais Louis, Dass Sajith, Kaltschmidt Julia A, Lopez-Schier Hernan, St Johnston Daniel, Brand Andrea H, Roth Siegfried, Guichet Antoine
Laboratory of Developmental Biology, Institut Jacques Monod, 2 place Jussieu, 75251 Paris Cedex 05, France.
Curr Biol. 2002 Dec 10;12(23):1971-81. doi: 10.1016/s0960-9822(02)01302-7.
The cytoskeleton and associated motors play an important role in the establishment of intracellular polarity. Microtubule-based transport is required in many cell types for the asymmetric localization of mRNAs and organelles. A striking example is the Drosophila oocyte, where microtubule-dependent processes govern the asymmetric positioning of the nucleus and the localization to distinct cortical domains of mRNAs that function as cytoplasmic determinants. A conserved machinery for mRNA localization and nuclear positioning involving cytoplasmic Dynein has been postulated; however, the precise role of plus- and minus end-directed microtubule-based transport in axis formation is not yet understood.
Here, we show that mRNA localization and nuclear positioning at mid-oogenesis depend on two motor proteins, cytoplasmic Dynein and Kinesin I. Both of these microtubule motors cooperate in the polar transport of bicoid and gurken mRNAs to their respective cortical domains. In contrast, Kinesin I-mediated transport of oskar to the posterior pole appears to be independent of Dynein. Beside their roles in RNA transport, both motors are involved in nuclear positioning and in exocytosis of Gurken protein. Dynein-Dynactin complexes accumulate at two sites within the oocyte: around the nucleus in a microtubule-independent manner and at the posterior pole through Kinesin-mediated transport.
The microtubule motors cytoplasmic Dynein and Kinesin I, by driving transport to opposing microtubule ends, function in concert to establish intracellular polarity within the Drosophila oocyte. Furthermore, Kinesin-dependent localization of Dynein suggests that both motors are components of the same complex and therefore might cooperate in recycling each other to the opposite microtubule pole.
细胞骨架及相关的分子马达在细胞内极性的建立中发挥着重要作用。在许多细胞类型中，基于微管的运输对于mRNA和细胞器的不对称定位是必需的。一个显著的例子是果蝇卵母细胞，其中依赖微管的过程控制着细胞核的不对称定位以及作为细胞质决定因子的mRNA在不同皮质区域的定位。已经推测存在一种涉及细胞质动力蛋白的保守的mRNA定位和核定位机制；然而，基于微管正端和负端运输在轴形成中的精确作用尚不清楚。
在这里，我们表明在卵子发生中期的mRNA定位和核定位依赖于两种分子马达，即细胞质动力蛋白和驱动蛋白I。这两种基于微管的分子马达在将bicoid和gurken mRNA极性运输到它们各自的皮质区域中协同作用。相比之下，驱动蛋白I介导的oskar向后极的运输似乎独立于动力蛋白。除了在RNA运输中的作用外，这两种分子马达都参与核定位和Gurken蛋白的胞吐作用。动力蛋白-动力蛋白激活蛋白复合物在卵母细胞内的两个位点积累：以不依赖微管的方式围绕细胞核，以及通过驱动蛋白介导的运输在后极积累。
微管分子马达细胞质动力蛋白和驱动蛋白I通过驱动向相反微管末端的运输，协同作用以在果蝇卵母细胞内建立细胞内极性。此外，依赖驱动蛋白的动力蛋白定位表明这两种分子马达是同一复合物的组成部分，因此可能在将彼此循环到相反的微管极方面协同作用。
