Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse.
Cohesin Removal along the Chromosome Arms during the First Meiotic Division Depends on a NEK1-PP1γ-WAPL Axis in the Mouse.
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DOI：
10.1016/j.celrep.2016.09.059
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发表时间：
2016-10-18
期刊：
影响因子：
8.8
通讯作者：
Holloway JK
中科院分区：
文献类型：
--
作者：
Brieño-Enríquez MA;Moak SL;Toledo M;Filter JJ;Gray S;Barbero JL;Cohen PE;Holloway JK
哺乳动物NIMA样激酶-1（NEK 1）是一种双特异性激酶，在小鼠生殖细胞减数分裂前期Ⅰ高度表达。NEK 1的缺失诱导在减数分裂前期I染色体上粘着蛋白的保留。及时沉积和去除粘连蛋白对于准确的染色体分离是必不可少的。两个过程调节粘附素的去除：涉及WAPL、Sororin和PDS 5 B的非蛋白水解机制和Separase的直接切割。在此，我们证明了NEK 1在减数分裂前期I期间WAPL加载的调节中的作用，通过NEK 1和PDS 5 B之间的相互作用。NEK 1-PDS 5 B对WAPL的调节由蛋白磷酸酶PP 1 γ介导，PP 1 γ既与NEK 1相互作用，又是NEK 1的磷酸靶点。综上所述，我们的研究结果表明，NEK 1磷酸化PP 1 γ，导致WAPL的去磷酸化，这反过来又导致其保留在染色体核心上，促进哺乳动物前期I结束时凝聚力的丧失。
Mammalian NIMA-like kinase-1 (NEK1) is a dual-specificity kinase highly expressed in mouse germ cells during prophase I of meiosis. Loss of NEK1 induces retention of cohesin on chromosomes at meiotic prophase I. Timely deposition and removal of cohesin is essential for accurate chromosome segregation. Two processes regulate cohesin removal: a non-proteolytic mechanism involving WAPL, Sororin, and PDS5B and direct cleavage by Separase. Herein, we demonstrate a role for NEK1 in the regulation of WAPL loading during meiotic prophase I, via an interaction between NEK1 and PDS5B. This regulation of WAPL by NEK1-PDS5B is mediated by the protein phosphatase PP1γ, which both interacts with, and is a phosphotarget, of NEK1. Taken together, our results reveal that NEK1 phosphorylates PP1γ leading to dephosphorylation of WAPL, which in turn results in its retention on chromosome cores to promote loss of cohesion at the end of prophase I in mammals.
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