nature20121213-11

Mark Petronczki及其同事提供了一个结构和功能分析结果,他们发现中央纺锤体蛋白(纺锤体中间区域和中间体中的一个蛋白复合物)是有丝分裂纺锤体与胞质膜间所缺失的联系环节,这个联系环节确保“胞质分裂”过程的最后结果。

-2012年12月13日《自然》


中文翻译


【题目】胞质分裂期间中部纺锤体蛋白将有丝分裂纺锤体与质膜相连接

【译文】细胞分裂末期,胞质分裂将新生子细胞的细胞质分隔开,并区分了分离的姐妹基因组。为了证实细胞分裂伴随染色体分离,有丝分裂纺锤体在细胞被膜水平控制细胞动力学事件。有丝分裂纺锤体刺激卵裂沟肌动球蛋白驱动的收缩,这种收缩直到在中央具有中间体的微管富余的胞间桥形成后才产生。中间体指导最终膜脱落反应,并被认为把剪接沟放入胞间桥。胞质分裂期间,有丝分裂纺锤体是如何被连接到质膜上的,还不清楚。本研究鉴定了中部纺锤体蛋白复合物中一种质膜圈合活性,该复合物是有丝分裂纺锤体和中间体的保守组分。我们证实了中部纺锤体蛋白亚单位MgcRacGAP的C1结构域通过与多阴离子磷脂肌醇脂质相互作用而与质膜相关。利用X射线结晶技术,我们解析了非典型C1结构域的结构。疏水帽的突变和MgcRacGAP C1结构域基本残基中的突变会阻碍蛋白与质膜的相关性,并消除人和鸡细胞中胞质分裂。缺乏MgcRacGAP C1结构域时,中部纺锤体蛋白的人工膜圈合恢复了细胞分裂。尽管C1结构域的功能对于中间区和中间体的形成并不是必要的,但它可以促进收缩性,对于质膜对中间体的粘附是必需的,这是这种细胞器长期公认的功能。我们的分析表明动物细胞中胞质分裂期间,中部纺锤体蛋白将有丝分裂纺锤体与质膜相连接,以固定最终的切割。

英文原稿


[Title]: Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis

[Authors]:Sergey Lekomtsev1 Kuan-Chung Su1 Valerie E. Pye2 Ken Blight3 Sriramkumar Sundaramoorthy1

Tohru Takaki1 Lucy M. Collinson3 Peter Cherepanov2 Nullin Divecha4 Mark Petronczki1

[Abstract]At the end of cell division, cytokinesis splits the cytoplasm of nascent daughter cells and partitions segregated sister genomes. To coordinate cell division with chromosome segregation, the mitotic spindle controls cytokinetic events at the cell envelope. The spindle midzone stimulates the actomyosin-driven contraction of the cleavage furrow, which proceeds until the formation of a microtubule-rich intercellular bridge with the midbody at its centre. The midbody directs the final membrane abscission reaction and has been proposed to attach the cleavage furrow to the intercellular bridge. How the mitotic spindle is connected to the plasma membrane during cytokinesis is not understood. Here we identify a plasma membrane tethering activity in the centralspindlin protein complex, a conserved component of the spindle midzone and midbody. We demonstrate that the C1 domain of the centralspindlin subunit MgcRacGAP associates with the plasma membrane by interacting with polyanionic phosphoinositide lipids. Using X-ray crystallography we determine the structure of this atypical C1 domain. Mutations in the hydrophobic cap and in basic residues of the C1 domain of MgcRacGAP prevent association of the protein with the plasma membrane, and abrogate cytokinesis in human and chicken cells. Artificial membrane tethering of centralspindlin restores cell division in the absence of the C1 domain of MgcRacGAP. Although C1 domain function is dispensable for the formation of the midzone and midbody, it promotes contractility and is required for the attachment of the plasma membrane to the midbody, a long-postulated function of this organelle. Our analysis suggests that centralspindlin links the mitotic spindle to the plasma membrane to secure the final cut during cytokinesis in animal cells.

原文地址

http://www.nature.com/nature/journal/v492/n7428/full/nature11773.html

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