Phosphorylation of CHO1 by Lats1/2 regulates the centrosomal activation of LIMK1 during cytokinesis
Phosphorylation of CHO1 by Lats1/2 regulates the centrosomal activation of LIMK1 during cytokinesis
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DOI：
10.1080/15384101.2015.1026489
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发表时间：
2015-05-19
期刊：
影响因子：
4.3
通讯作者：
Nojima, Hiroshi
中科院分区：
文献类型：
--
作者：
Okamoto, Ayumi;Yabuta, Norikazu;Nojima, Hiroshi
大肿瘤抑制因子1和2（Lats 1/2）调节中心体的完整性，染色体分离和胞质分裂。作为中枢纺锤体复合物的组成部分，驱动蛋白样蛋白CHO 1及其剪接变体MKLP 1与染色体过客蛋白和GTP酶共定位，并调节收缩环的形成和胞质分裂;然而，CHO 1/MKLP 1的调节机制仍然难以捉摸。在这里，我们表明，Lats 1/2磷酸化Ser 716的F-肌动蛋白相互作用区域的CHO 1，这是缺席MKLP 1。磷酸化CHO 1定位于中心体和中间体，肌动蛋白聚合因子LIMK 1（LIMK 1）被鉴定为其结合伴侣。组成性磷酸化和非磷酸化的CHO 1的过表达改变了HeLa细胞中LIMK 1在中心体的有丝分裂定位和激活，导致通过Cofilin的过度磷酸化和Ect 2的错误定位抑制胞质分裂。这些结果表明Lats 1/2通过调节中心体上CHO 1的磷酸化和LIMK 1的有丝分裂激活来严格控制胞质分裂。
Large tumor suppressor 1 and 2 (Lats1/2) regulate centrosomal integrity, chromosome segregation and cytokinesis. As components of the centralspindlin complex, the kinesin-like protein CHO1 and its splicing variant MKLP1 colocalize with chromosome passenger proteins and GTPases and regulate the formation of the contractile ring and cytokinesis; however, the regulatory mechanisms of CHO1/MKLP1 remain elusive. Here, we show that Lats1/2 phosphorylate Ser716 in the F-actin-interacting region of CHO1, which is absent in MKLP1. Phosphorylated CHO1 localized to the centrosomes and midbody, and the actin polymerization factor LIM-kinase 1 (LIMK1) was identified as its binding partner. Overexpression of constitutively phosphorylated and non-phosphorylated CHO1 altered the mitotic localization and activation of LIMK1 at the centrosomes in HeLa cells, leading to the inhibition of cytokinesis through excessive phosphorylation of Cofilin and mislocalization of Ect2. These results suggest that Lats1/2 stringently control cytokinesis by regulating CHO1 phosphorylation and the mitotic activation of LIMK1 on centrosomes.