Cdk1-dependent phosphoinhibition of a formin-F-BAR interaction opposes cytokinetic contractile ring formation.
Cdk1-dependent phosphoinhibition of a formin-F-BAR interaction opposes cytokinetic contractile ring formation.
复制标题
Cdk1 依赖性磷酸化抑制福尔明-F-BAR 相互作用，反对细胞因子收缩环的形成。
DOI：
10.1091/mbc.e17-11-0646
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发表时间：
2018
影响因子：
3.3
通讯作者：
Gould,KathleenL
中科院分区：
文献类型：
--
作者：
Willet,AlainaH;Bohnert,KAdam;Gould,KathleenL
裂殖酵母胞质分裂需要肌动球蛋白收缩环（CR）的组装和收缩。有丝分裂开始时，一个单一的必需蛋白Cdc 12定位于细胞中部，并使CR的F-肌动蛋白成核。Cdc 12中间募集部分通过其与F-BAR支架Cdc 15的直接结合来介导。鉴于Cdc 12在M期过度磷酸化，我们探讨了Cdc 12磷酸化调节是否影响其在有丝分裂期间与Cdc 15的关联。我们发现，Cdk 1，一个主要的有丝分裂激酶，磷酸化Cdc 12的6个N-末端残基附近的Cdc 15结合位点，这些网站上的磷酸化抑制其与Cdc 15 F-BAR域的相互作用。与这一发现相一致的是，所有6个Cdk 1位点均变为磷酸化模拟残基（cdc 12 -6D）的acdc 12突变体显示出与cdc 12-P31 A相似的表型，其中Cdc 15结合基序被破坏;两者均显示CR处Cdc 12减少和CR形成延迟。总之，这些结果表明，Cdc 12的Cdk 1磷酸化拮抗其与Cdc 15的相互作用，从而反对Cdc 12的CR定位。这些结果与Cdk 1在抑制胞质分裂中的一般作用一致，直到染色体分离完成。
InSchizosaccharomyces pombe, cytokinesis requires the assembly and constriction of an actomyosin-based contractile ring (CR). A single essential formin, Cdc12, localizes to the cell middle upon mitotic onset and nucleates the F-actin of the CR. Cdc12 medial recruitment is mediated in part by its direct binding to the F-BAR scaffold Cdc15. Given that Cdc12 is hyperphosphorylated in M phase, we explored whether Cdc12 phosphoregulation impacts its association with Cdc15 during mitosis. We found that Cdk1, a major mitotic kinase, phosphorylates Cdc12 on six N-terminal residues near the Cdc15-binding site, and phosphorylation on these sites inhibits its interaction with the Cdc15 F-BAR domain. Consistent with this finding, acdc12mutant with all six Cdk1 sites changed to phosphomimetic residues (cdc12-6D) displays phenotypes similar tocdc12-P31A, in which the Cdc15-binding motif is disrupted; both show reduced Cdc12 at the CR and delayed CR formation. Together, these results indicate that Cdk1 phosphorylation of formin Cdc12 antagonizes its interaction with Cdc15 and thereby opposes Cdc12’s CR localization. These results are consistent with a general role for Cdk1 in inhibiting cytokinesis until chromosome segregation is complete.