Dynamic localization of LIN-5 and GPR-1/2 to cortical force generation domains during spindle positioning

Dynamic localization of LIN-5 and GPR-1/2 to cortical force generation domains during spindle positioning
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DOI:
10.1016/j.ydbio.2007.11.037
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发表时间:
2008-03-01
影响因子:
2.7
通讯作者:
Rose, Lesilee S.
Rose, Lesilee S.
中科院分区:
生物学3区
文献类型:
--
作者:
Park, Dae Hwi;Rose, Lesilee S.

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在许多系统中,G蛋白信号通路调节有丝分裂纺锤体的定位。在秀丽隐杆线虫胚胎中,G α亚基与正调节因子GPR-1/2和LIN-5一起作用,在第一次不对称分裂过程中产生皮层拉力,导致后纺锤体位移。GPR-1/2此时通过PAR极性线索不对称地定位于后皮层。本研究表明,在纺锤体移位过程中,LIN-5与GPR-1/2在单细胞胚胎中共定位。值得注意的是,我们还发现LIN-5和GPR-1/2以极性依赖的方式定位于相反的前皮层,在核集中和旋转运动中,形成纺锤体朝向极性轴。LIN-5或GPR-1/2的耗竭导致集中和旋转速率下降,表明在这一阶段力的产生中起作用。LIN-5和GPR-1/2的定位在很大程度上是相互依赖的,需要Got。此外,LIN-5在体内与Ga一起免疫沉淀,这种关联依赖于GPR-1/2。这些结果表明,G α /GPR-1/2/LIN-5复合物在响应极性信号时是不对称定位的,这可能是在核旋转和主轴位移过程中向力产生机制传递不对称的主动信号复合物。(C) 2007爱思唯尔公司版权所有。
G protein signaling pathways regulate mitotic spindle positioning during cell division in many systems. In Caenorhabditis elegans embryos, G alpha subunits act with the positive regulators GPR-1/2 and LIN-5 to generate cortical pulling forces for posterior spindle displacement during the first asymmetric division. GPR-1/2 are asymmetrically localized at the posterior cortex by PAR polarity cues at this time. Here we show that LIN-5 colocalizes with GPR-1/2 in one-cell embryos during spindle displacement. Significantly, we also find that LIN-5 and GPR-1/2 are localized to the opposite, anterior cortex in a polarity-dependent manner during the nuclear centration and rotation movements that orient the forming spindle onto the polarity axis. The depletion of LIN-5 or GPR-1/2 results in decreased centration and rotation rates, indicating a role in force generation at this stage. The localization of LIN-5 and GPR-1/2 is largely interdependent and requires Got. Further, LIN-5 immunoprecipitates with Ga in vivo, and this association is GPR-1/2 dependent. These results suggest that a complex of G alpha/GPR-1/2/LIN-5 is asymmetrically localized in response to polarity cues, and this may be the active signaling complex that transmits asymmetries to the force generation machinery during both nuclear rotation and spindle displacement. (C) 2007 Elsevier Inc. All rights reserved.