Calcineurin activity is required for the completion of cytokinesis
Calcineurin activity is required for the completion of cytokinesis
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DOI：
10.1007/s00018-010-0401-z
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发表时间：
2010-11-01
影响因子：
8
通讯作者：
Robinson, Phillip J.
中科院分区：
文献类型：
--
作者：
Chircop, Megan;Malladi, Chandra S.;Robinson, Phillip J.
细胞分裂的成功完成需要蛋白磷酸化的时空调节以及蛋白激酶和磷酸酶的协调活动。许多有丝分裂蛋白激酶被很好地表征，而有丝分裂磷酸酶在很大程度上是未知的。在这里，我们表明钙(2+)-和钙调素依赖性磷酸酶，钙调神经磷酸酶（CaN），是哺乳动物细胞分裂所必需的，在脱落阶段特异性地起作用。CaN抑制剂在HeLa细胞中诱导多核，并延长细胞通过延长的细胞内桥连接的时间。当细胞分裂过程中Ca（2+）内流时，CaN被激活，靶向一组蛋白去磷酸化，包括动力蛋白II （dynII）。在细胞内桥，phospho-dynII和CaN共定位于位于中央中间环两侧的双侧翼中间环（FMRs）。CaN活性和FMRs的分解与脱落一致。因此，CaN在哺乳动物细胞中体的活性在调节细胞分裂完成过程中起着关键作用。
Successful completion of cytokinesis requires the spatio-temporal regulation of protein phosphorylation and the coordinated activity of protein kinases and phosphatases. Many mitotic protein kinases are well characterized while mitotic phosphatases are largely unknown. Here, we show that the Ca(2+)- and calmodulin-dependent phosphatase, calcineurin (CaN), is required for cytokinesis in mammalian cells, functioning specifically at the abscission stage. CaN inhibitors induce multinucleation in HeLa cells and prolong the time cells spend connected via an extended intracellular bridge. Upon Ca(2+) influx during cytokinesis, CaN is activated, targeting a set of proteins for dephosphorylation, including dynamin II (dynII). At the intracellular bridge, phospho-dynII and CaN are co-localized to dual flanking midbody rings (FMRs) that reside on either side of the central midbody ring. CaN activity and disassembly of the FMRs coincide with abscission. Thus, CaN activity at the midbody plays a key role in regulating the completion of cytokinesis in mammalian cells.