Kif18a is specifically required for mitotic progression during germ line development.
Kif18a is specifically required for mitotic progression during germ line development.
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DOI：
10.1016/j.ydbio.2015.03.011
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发表时间：
2015-06-15
影响因子：
2.7
通讯作者：
Reinholdt, Laura G.
中科院分区：
文献类型：
--
作者：
Czechanski, Anne;Kim, Haein;Byers, Candice;Greenstein, Ian;Stumpff, Jason;Reinholdt, Laura G.
生殖系发育中的基因组完整性是繁殖力的严格要求。在增殖的体细胞和生殖细胞中，有丝分裂检查点机制确保准确的染色体分离和整倍性。有越来越多的证据表明，有丝分裂细胞周期的组成部分是唯一需要在生殖细胞系，以确保基因组的完整性。我们以前表明，主要表型的生殖细胞缺陷2（gcd 2）突变小鼠是不育，由于在胚胎发育过程中的生殖细胞耗竭。在这里，我们表明，潜在的突变是一个错义突变，R308 K，在运动域的驱动蛋白-8家族成员，KIF 18 A，一种蛋白质，在各种增殖组织中表达，是一个关键的调控染色体排列在有丝分裂。尽管突变的保守性，我们表明，其功能的后果相当于KIF 18 A在HeLa细胞中的缺陷。我们还表明，体细胞通过有丝分裂的进展，尽管有染色体排列缺陷，而生殖细胞与类似的染色体排列缺陷进行有丝分裂停滞和凋亡。我们的数据为生殖细胞和体细胞中染色体对齐的差异要求提供了证据，并表明Kif 18 a是增殖生殖细胞中细胞周期进展所需的越来越多的基因之一。
Genome integrity in the developing germ line is strictly required for fecundity. In proliferating somatic cells and in germ cells, there are mitotic checkpoint mechanisms that ensure accurate chromosome segregation and euploidy. There is growing evidence of mitotic cell cycle components that are uniquely required in the germ line to ensure genome integrity. We previously showed that the primary phenotype of germ cell deficient 2 (gcd2) mutant mice is infertility due to germ cell depletion during embryogenesis. Here we show that the underlying mutation is a mis-sense mutation, R308K, in the motor domain of the kinesin-8 family member, KIF18A, a protein that is expressed in a variety of proliferative tissues and is a key regulator of chromosome alignment during mitosis. Despite the conservative nature of the mutation, we show that its functional consequences are equivalent to KIF18A deficiency in HeLa cells. We also show that somatic cells progress through mitosis, despite having chromosome alignment defects, while germ cells with similar chromosome alignment defects undergo mitotic arrest and apoptosis. Our data provide evidence for differential requirements for chromosome alignment in germ and somatic cells and show that Kif18a is one of a growing number of genes that are specifically required for cell cycle progression in proliferating germ cells.
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影响因子：
3.6
作者：
Lu, B;Bishop, CE
通讯作者：
Bishop, CE
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影响因子：
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作者：
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9.2
作者：
Waters, JC;Chen, RH;Nicklas, RB
通讯作者：
Nicklas, RB