The ARP2/3 complex prevents excessive formin activity during cytokinesis.
The ARP2/3 complex prevents excessive formin activity during cytokinesis.
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DOI：
10.1091/mbc.e18-07-0471
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Carvalho AX
中科院分区：
文献类型：
--
作者：
Chan FY;Silva AM;Saramago J;Pereira-Sousa J;Brighton HE;Pereira M;Oegema K;Gassmann R;Carvalho AX
胞质分裂通过收缩肌球蛋白收缩环来完成细胞分裂，肌球蛋白收缩环将两个子细胞分开。在这里，我们使用早期秀丽隐杆线虫胚胎来探索环状和周围皮质中的肌动蛋白细丝网络是如何受到单个胞质分裂形式Cyk-1和Arp2/3复合体的调节的，这两个复合体分别形成了未分枝和分枝的细丝。我们表明，Cyk-1和Arp2/3复合体是主要的F-肌动蛋白核因子，负责产生不同的皮质F-肌动蛋白结构，其中任何一个核因子的耗尽都会影响细胞质分裂的动力学。Cyk-1对收缩环中正常的F-肌动蛋白水平至关重要，在皱纹进入后，对Cyk-1的急性抑制会减缓环收缩速度，这表明在整个环收缩过程中都需要Cyk-1的活性。令人惊讶的是，虽然Arp2/3复合体不位于收缩环中，但Arp2亚单位的耗尽或Arp2/3复合体抑制剂的处理延迟了收缩环的形成和收缩。我们提出的证据表明，延迟是由于形成核皮层F-肌动蛋白过量所致，表明Arp2/3复合体负向调节Cyk-1的活性。我们的结论是，胞质分裂的动力学受两个主要肌动蛋白细丝核子之间的相互作用所调节。
Cytokinesis completes cell division by constriction of an actomyosin contractile ring that separates the two daughter cells. Here we use the early Caenorhabditis elegans embryo to explore how the actin filament network in the ring and the surrounding cortex is regulated by the single cytokinesis formin CYK-1 and the ARP2/3 complex, which nucleate nonbranched and branched filaments, respectively. We show that CYK-1 and the ARP2/3 complex are the predominant F-actin nucleators responsible for generating distinct cortical F-actin architectures and that depletion of either nucleator affects the kinetics of cytokinesis. CYK-1 is critical for normal F-actin levels in the contractile ring, and acute inhibition of CYK-1 after furrow ingression slows ring constriction rate, suggesting that CYK-1 activity is required throughout ring constriction. Surprisingly, although the ARP2/3 complex does not localize in the contractile ring, depletion of the ARP2 subunit or treatment with ARP2/3 complex inhibitor delays contractile ring formation and constriction. We present evidence that the delays are due to an excess in formin-nucleated cortical F-actin, suggesting that the ARP2/3 complex negatively regulates CYK-1 activity. We conclude that the kinetics of cytokinesis are modulated by interplay between the two major actin filament nucleators.