Mitchison Timothy J, Field Christine M
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115.
Marine Biological Laboratory, Woods Hole, Massachusetts 02543.
Cold Spring Harb Symp Quant Biol. 2017;82:165-171. doi: 10.1101/sqb.2017.82.033654. Epub 2017 Dec 1.
During cytokinesis, the mitotic spindle communicates with the cell cortex to position a cleavage furrow that will cut through the cell in the plane defined by the metaphase plate. We investigated the molecular basis of this communication in eggs, where the signal has to travel ∼400 µm in ∼30 min to reach the cortex from the first anaphase spindle. At anaphase onset, huge microtubule asters grow out from the poles of the spindle and meet at the plane previously defined by the metaphase plate. This disc-shaped boundary plane recruits the chromosome passenger complex (CPC) and centralspindlin to antiparallel microtubule bundles. It grows out to the cell cortex as the asters expand, where it induces the furrow. CPC and centralspindlin were not recruited to boundaries between asters from different spindles, suggesting a role of chromatin in triggering the CPC-positive state. Recruitment of CPC to aster boundaries was reconstituted in an extract system, and we observed that recruitment was stimulated by proximity to chromatin. Finally, we discuss models for molecular processes involved in initiation and growth of the CPC-positive disc that communicates the position of the metaphase plate to the cortex over hundreds of micrometers in frog eggs.
在胞质分裂过程中,有丝分裂纺锤体与细胞皮层进行通讯,以定位一条分裂沟,该分裂沟将在中期板所确定的平面上穿过细胞。我们研究了卵子中这种通讯的分子基础,在卵子中,信号必须在约30分钟内传播约400微米才能从第一个后期纺锤体到达皮层。在后期开始时,巨大的微管星体从纺锤体的两极长出,并在先前由中期板确定的平面上相遇。这个盘状的边界平面将染色体乘客复合体(CPC)和中央纺锤体募集到反平行微管束上。随着星体的扩展,它向外延伸到细胞皮层,在那里诱导形成分裂沟。CPC和中央纺锤体没有被募集到来自不同纺锤体的星体之间的边界,这表明染色质在触发CPC阳性状态中起作用。在一个提取物系统中重建了CPC向星体边界的募集,并且我们观察到募集受到与染色质接近程度的刺激。最后,我们讨论了在青蛙卵子中,将中期板的位置传递到数百微米外的皮层的CPC阳性盘的起始和生长所涉及的分子过程模型。