PRC1 controls spindle polarization and recruitment of cytokinetic factors during monopolar cytokinesis.
PRC1 controls spindle polarization and recruitment of cytokinetic factors during monopolar cytokinesis.
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DOI：
10.1091/mbc.e11-12-1008
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发表时间：
2012-04
影响因子：
3.3
通讯作者：
Shuster CB
中科院分区：
文献类型：
--
作者：
Shrestha S;Wilmeth LJ;Eyer J;Shuster CB
PRC1和KIF4A被认为在组织中央纺锤体的反平行微管中起关键作用。使用纺锤体双极性受损的细胞发现了这些蛋白质的可分离和非冗余作用，其中细胞分裂可以通过绕过纺锤体组装检查点诱导。中央纺锤体是一个后期微管阵列，在组织细胞分裂的信号机制中起着重要作用。中央纺锤体组织细胞动力学装置的模型以微管的反平行排列为前提，然而缺乏纺锤体双极性的细胞在被迫进入有丝分裂出口时能够产生远端异位沟槽。由于细胞分裂蛋白调节因子（PRC1）和细胞分裂蛋白家族成员4A （KIF4A）被认为在组织反平行中间区阵列中起主要作用，我们试图阐明它们在单极细胞分裂中的作用。虽然这两个因子在单极细胞分裂过程中都定位于微管的远端，但PRC1和KIF4A的缺失表现出不同的表型。有丝分裂退出后，PRC1缺失的细胞无法形成极化微管阵列或异位沟，Aurora B激酶、雄性生殖细胞Rac gtpase激活蛋白和RhoA向皮质的募集受损。相比之下，KIF4A缺失既不损害极化也不损害异位沟，但它确实导致纺锤体延长，细胞动力学因子弥漫性分布。因此，即使在没有纺锤体双极性的情况下，PRC1似乎对于极化平行微管和集中负责收缩环组装的因素至关重要，而KIF4A则需要限制后期微管的长度。
PRC1 and KIF4A are believed to play a critical role in organizing antiparallel microtubules of the central spindle. Separable and nonredundant roles for these proteins were uncovered using cells with compromised spindle bipolarity, in which cytokinesis can be induced by bypassing the spindle assembly checkpoint. The central spindle is a postanaphase array of microtubules that plays an essential role in organizing the signaling machinery for cytokinesis. The model by which the central spindle organizes the cytokinetic apparatus is premised on an antiparallel arrangement of microtubules, yet cells lacking spindle bipolarity are capable of generating a distal domain of ectopic furrowing when forced into mitotic exit. Because protein regulator of cytokinesis (PRC1) and kinesin family member 4A (KIF4A) are believed to play a principal role in organizing the antiparallel midzone array, we sought to clarify their roles in monopolar cytokinesis. Although both factors localized to the distal ends of microtubules during monopolar cytokinesis, depletion of PRC1 and KIF4A displayed different phenotypes. Cells depleted of PRC1 failed to form a polarized microtubule array or ectopic furrows following mitotic exit, and recruitment of Aurora B kinase, male germ cell Rac GTPase-activating protein, and RhoA to the cortex was impaired. In contrast, KIF4A depletion impaired neither polarization nor ectopic furrowing, but it did result in elongated spindles with a diffuse distribution of cytokinetic factors. Thus, even in the absence of spindle bipolarity, PRC1 appears to be essential for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly, whereas KIF4A is required for limiting the length of anaphase microtubules.