Nguyen-Ngoc Tu, Afshar Katayoun, Gönczy Pierre
Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology (EPFL), School of Life Sciences, Lausanne, Switzerland CH-1066.
Nat Cell Biol. 2007 Nov;9(11):1294-302. doi: 10.1038/ncb1649. Epub 2007 Oct 5.
Despite being essential for spatial cell division control, the mechanisms governing spindle positioning remain incompletely understood. In the Caenorhabditis elegans one-cell stage embryo, the spindle becomes asymmetrically positioned during anaphase through the action of as-yet unidentified cortical force generators that pull on astral microtubules and that depend on two G alpha proteins and associated proteins. We performed spindle-severing experiments following temporally restricted gene inactivation and drug exposure, and established that microtubule dynamics and dynein are both required for generating efficient pulling forces. We found that the G alpha-associated proteins GPR-1/2 and LIN-5 interact in vivo with LIS-1, a component of the dynein complex. Moreover, we discovered that the LIN-5, GPR-1/2 and the G alpha proteins promote the presence of the dynein complex at the cell cortex. Our findings suggest a mechanism by which the G alpha proteins enable GPR-1/2 and LIN-5 recruitment to the cortex, thus ensuring the presence of cortical dynein. Together with microtubule dynamics, this allows pulling forces to be exerted and proper cell division to be achieved.
尽管纺锤体定位对于空间细胞分裂控制至关重要,但其调控机制仍未完全明晰。在秀丽隐杆线虫的单细胞期胚胎中,纺锤体在后期通过尚未明确的皮质力产生器的作用而不对称定位,这些力产生器牵拉星体微管,且依赖于两种Gα蛋白及相关蛋白。我们在进行时间限制的基因失活和药物处理后开展了纺锤体切断实验,并确定微管动力学和动力蛋白对于产生有效的牵拉力量均是必需的。我们发现,与Gα相关的蛋白GPR - 1/2和LIN - 5在体内与动力蛋白复合体的一个组分LIS - 1相互作用。此外,我们还发现LIN - 5、GPR - 1/2和Gα蛋白促进动力蛋白复合体在细胞皮质的存在。我们的研究结果提示了一种机制,即Gα蛋白使GPR - 1/2和LIN - 5募集至皮质,从而确保皮质动力蛋白的存在。与微管动力学一起,这使得能够施加牵拉力量并实现正确的细胞分裂。