Delineating the contribution of Spc105-bound PP1 to spindle checkpoint silencing and kinetochore microtubule attachment regulation.
Delineating the contribution of Spc105-bound PP1 to spindle checkpoint silencing and kinetochore microtubule attachment regulation.
复制标题
描述 Spc105 结合 PP1 对纺锤体检查点沉默和动粒微管附着调节的贡献。
DOI：
10.1083/jcb.201810172
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Joglekar,AjitP
中科院分区：
文献类型：
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作者：
Roy,Babhrubahan;Verma,Vikash;Sim,Janice;Fontan,Adrienne;Joglekar,AjitP
在细胞分裂过程中，准确的染色体分离需要纺锤体组件检查点(SAC)和错误的纠错机制，SAC可以检测未连接的动粒-微管连接，从而破坏不正确的动粒-微管连接。虽然SAC和纠错都受到蛋白磷酸酶1(PP1)的调节，PP1可以沉默SAC并稳定动粒-微管连接，但这些不同的PP1功能是如何协调的仍不清楚。在这里，我们研究了PP1，停靠在其保守的动粒受体Spc105/Knl1上，对SAC沉默和附着调节的贡献。我们发现，Spc105结合的PP1对于SAC沉默是关键的，但对于纠错来说是必不可少的；事实上，减少PP1在Spc105上的对接改善了染色体分离和突变/应激状态的生存能力。此外，我们还表明，在染色体双向定位之前而不是在染色体双向定位之后，人为地将PP1重新招募到Spc105/Knl1会干扰纠错。这些观察导致我们建议，PP1到Spc105/Knl1的招募受到仔细的调控，以确保染色体双向定位先于SAC沉默，从而确保准确的染色体分离。
Accurate chromosome segregation during cell division requires the spindle assembly checkpoint (SAC), which detects unattached kinetochores, and an error correction mechanism that destabilizes incorrect kinetochore–microtubule attachments. While the SAC and error correction are both regulated by protein phosphatase 1 (PP1), which silences the SAC and stabilizes kinetochore–microtubule attachments, how these distinct PP1 functions are coordinated remains unclear. Here, we investigate the contribution of PP1, docked on its conserved kinetochore receptor Spc105/Knl1, to SAC silencing and attachment regulation. We find that Spc105-bound PP1 is critical for SAC silencing but dispensable for error correction; in fact, reduced PP1 docking on Spc105 improved chromosome segregation and viability of mutant/stressed states. We additionally show that artificially recruiting PP1 to Spc105/Knl1 before, but not after, chromosome biorientation interfered with error correction. These observations lead us to propose that recruitment of PP1 to Spc105/Knl1 is carefully regulated to ensure that chromosome biorientation precedes SAC silencing, thereby ensuring accurate chromosome segregation.