Colombo Kelly, Grill Stephan W, Kimple Randall J, Willard Francis S, Siderovski David P, Gönczy Pierre
Swiss Institute for Experimental Cancer Research (ISREC), 1066 Epalinges/Lausanne, Switzerland.
Science. 2003 Jun 20;300(5627):1957-61. doi: 10.1126/science.1084146. Epub 2003 May 15.
Asymmetric divisions are crucial for generating cell diversity; they rely on coupling between polarity cues and spindle positioning, but how this coupling is achieved is poorly understood. In one-cell stage Caenorhabditis elegans embryos, polarity cues set by the PAR proteins mediate asymmetric spindle positioning by governing an imbalance of net pulling forces acting on spindle poles. We found that the GoLoco-containing proteins GPR-1 and GPR-2, as well as the Galpha subunits GOA-1 and GPA-16, were essential for generation of proper pulling forces. GPR-1/2 interacted with guanosine diphosphate-bound GOA-1 and were enriched on the posterior cortex in a par-3- and par-2-dependent manner. Thus, the extent of net pulling forces may depend on cortical Galpha activity, which is regulated by anterior-posterior polarity cues through GPR-1/2.
不对称分裂对于产生细胞多样性至关重要;它们依赖于极性线索与纺锤体定位之间的耦合,但这种耦合是如何实现的却知之甚少。在单细胞阶段的秀丽隐杆线虫胚胎中,由PAR蛋白设定的极性线索通过控制作用于纺锤体极的净拉力不平衡来介导不对称纺锤体定位。我们发现,含有GoLoco的蛋白GPR-1和GPR-2,以及Gα亚基GOA-1和GPA-16,对于产生适当的拉力至关重要。GPR-1/2与结合鸟苷二磷酸的GOA-1相互作用,并以par-3和par-2依赖的方式富集在后皮质上。因此,净拉力的程度可能取决于皮质Gα活性,而皮质Gα活性由前后极性线索通过GPR-1/2进行调节。