Delineating the contribution of Spc105-bound PP1 to spindle checkpoint silencing and kinetochore microtubule attachment regulation

被引:18
|
作者
Roy, Babhrubahan [1 ]
Verma, Vikash [1 ]
Sim, Janice [1 ]
Fontan, Adrienne [1 ]
Joglekar, Ajit P. [1 ,2 ]
机构
[1] Univ Michigan, Dept Cell & Dev Biol, Med Sch, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Biophys, Ann Arbor, MI 48109 USA
来源
JOURNAL OF CELL BIOLOGY | 2019年 / 218卷 / 12期
基金
美国国家卫生研究院;
关键词
PROTEIN-KINASE; PHOSPHATASE; COMPLEX; MPS1; IDENTIFICATION; ARCHITECTURE; MECHANISMS; TARGETS; BINDING; KNL1;
D O I
10.1083/jcb.201810172
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:3926 / 3942
页数:17
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