Srinivasan Dayalan G, Fisk Ridgely M, Xu Huihong, van den Heuvel Sander
Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, USA.
Genes Dev. 2003 May 15;17(10):1225-39. doi: 10.1101/gad.1081203. Epub 2003 May 2.
The Caenorhabditis elegans coiled-coil protein LIN-5 mediates several processes in cell division that depend on spindle forces, including alignment and segregation of chromosomes and positioning of the spindle. Here, we describe two closely related proteins, GPR-1 and GPR-2 (G protein regulator), which associate with LIN-5 in vivo and in vitro and depend on LIN-5 for localization to the spindle and cell cortex. GPR-1/GPR-2 contain a GoLoco/GPR motif that mediates interaction with GDP-bound Galpha(i/o). Inactivation of lin-5, gpr-1/gpr-2, or the Galpha(i/o) genes goa-1 and gpa-16 all cause highly similar chromosome segregation and spindle positioning defects, indicating a positive role for the LIN-5 and GPR proteins in G protein signaling. The lin-5 and gpr-1/gpr-2 genes appear to act downstream of the par polarity genes in the one- and two-cell stages and downstream of the tyrosine kinase-related genes mes-1 and src-1 at the four-cell stage. Together, these results indicate that GPR-1/GPR-2 in association with LIN-5 activate G protein signaling to affect spindle force. Polarity determinants may regulate LIN-5/GPR/Galpha locally to create the asymmetric forces that drive spindle movement. Results in C. elegans and other species are consistent with a novel model for receptor-independent activation of Galpha(i/o) signaling.
秀丽隐杆线虫的卷曲螺旋蛋白LIN-5介导细胞分裂中依赖纺锤体力量的多个过程，包括染色体的排列和分离以及纺锤体的定位。在此，我们描述了两种密切相关的蛋白，GPR-1和GPR-2（G蛋白调节剂），它们在体内和体外均与LIN-5相关联，并依赖LIN-5定位于纺锤体和细胞皮层。GPR-1/GPR-2含有一个GoLoco/GPR基序，该基序介导与结合GDP的Gα(i/o)的相互作用。lin-5、gpr-1/gpr-2或Gα(i/o)基因goa-1和gpa-十六的失活均会导致高度相似的染色体分离和纺锤体定位缺陷，表明LIN-5和GPR蛋白在G蛋白信号传导中具有正向作用。lin-5和gpr-1/gpr-2基因似乎在单细胞和双细胞阶段位于par极性基因的下游，在四细胞阶段位于酪氨酸激酶相关基因mes-1和src-1的下游。这些结果共同表明，与LIN-5相关联的GPR-1/GPR-2激活G蛋白信号传导以影响纺锤体力量。极性决定因素可能局部调节LIN-5/GPR/Gα，以产生驱动纺锤体运动的不对称力量。秀丽隐杆线虫和其他物种的结果与一种不依赖受体激活Gα(i/o)信号传导的新模型一致。
