Table S1 from Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis

The chromosomal passenger complex (CPC) - composed of Aurora B kinase, Borealin, Survivin and INCENP - surveys the fidelity of genome segregation throughout cell division. The CPC has been proposed to prevent polyploidy by controlling the final separation or abscission, of the two daughter cells via regulation of the ESCRT-III CHMP4C component. The molecular details are, however, still unclear. Using atomic force microscopy, we show that CHMP4C binds to and remodels membranes <i>in vitro</i>. Borealin prevents the association of CHMP4C with membranes, whereas Aurora B interferes with CHMP4C's membrane remodelling activity. Moreover, we show that CHMP4C phosphorylation is not required for its assembly into spiral filaments at the abscission site and that two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesis. We also characterized the CHMP4C interactome in telophase cells and show that the centralspindlin complex associates preferentially with unphosphorylated CHMP4C in cytokinesis. Our findings indicate that gradual dephosphorylation of CHMP4C triggers a 'relay' mechanism between the CPC and centralspindlin that regulates the timely distribution and activation of CHMP4C for the execution of abscission.

染色体乘客复合体（chromosomal passenger complex, CPC）由极光B激酶（Aurora B kinase）、波瑞林（Borealin）、生存素（Survivin）以及内着丝粒蛋白（INCENP）组成，其在整个细胞分裂进程中监测基因组分离的保真度。已有研究提出，CPC可通过调控转运必需内体分选复合物III（ESCRT-III）的CHMP4C组分，控制两个子代细胞的最终分离即胞质分裂断离，从而防止多倍体的形成，但其具体分子机制仍未明确。本研究借助原子力显微镜（atomic force microscopy, AFM）证实，CHMP4C可在体外结合并重塑生物膜；其中波瑞林可阻碍CHMP4C与生物膜的结合，而极光B激酶则会抑制CHMP4C的膜重塑活性。此外，本研究证实，CHMP4C在胞质分裂断离位点组装为螺旋丝状纤维并不依赖其磷酸化修饰，且在胞质分裂过程中存在两个定位截然不同的磷酸化CHMP4C亚群。本研究还对有丝分裂末期细胞内的CHMP4C相互作用组进行了表征，并证实胞质分裂过程中中央纺锤体复合物（centralspindlin complex）优先与未磷酸化的CHMP4C结合。本研究结果表明，CHMP4C的逐步去磷酸化会触发CPC与中央纺锤体复合物之间的“中继”调控机制，该机制可精准调控CHMP4C的时序分布与激活，从而保障胞质分裂断离的顺利执行。