The highly conserved LAMMER/CLK2 protein kinases prevent germ cell overproliferation in Drosophila.
The highly conserved LAMMER/CLK2 protein kinases prevent germ cell overproliferation in Drosophila.
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DOI：
10.1016/j.ydbio.2013.01.023
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发表时间：
2013-04
影响因子：
2.7
通讯作者：
Shaowei Zhao;Di Chen;Q. Geng;Zhaohui Wang
中科院分区：
文献类型：
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作者：
Shaowei Zhao;Di Chen;Q. Geng;Zhaohui Wang
生殖细胞在进入减数分裂之前进行适当的有丝分裂扩增。有丝分裂/减数分裂开关驱动生殖细胞离开潜在的干细胞库并最终分化。这一重要过程在所有动物的精子发生中受到严格控制。然而，统一的机制尚未解开。果蝇精子发生是研究有丝分裂/减数分裂开关调控机制的理想系统。促分化因子Bam的及时积累已被证明是这一过程的核心。在果蝇遗传筛选中，我们发现编码高度保守的LAMMER/Cdc 2-like kinase（CLK）家族成员的基因Doa的突变可引起生殖细胞过度增殖，这是由于从有丝分裂到减数分裂的过渡失败所致。在Doa突变体生殖细胞中额外的Bam表达促进了从有丝分裂到减数分裂状态的分化。值得注意的是，人或鼠CLK 2可以防止生殖系过度增殖，甚至恢复Doa突变果蝇的生育能力。Doa或其人类同源物的这种拯救活性需要在其预测的激酶催化结构域中的保守残基。我们建议，LAMMER/Cdc 2样激酶，代表Doa和它的哺乳动物同系物CLK 2，是一个关键的和保守的组成部分，在有丝分裂到减数分裂开关的调节程序。
Germ cells undergo proper mitotic amplification before entering meiosis. The mitosis/meiosis switch drives the germ cells to leave the potential stem cell pool and become terminally differentiated. This important process is tightly controlled in the spermatogenesis of all animals. However, a unifying mechanism has yet to be unraveled. Drosophila spermatogenesis is an ideal system to dissect the regulatory program of the mitosis/meiosis switch. The timely accumulation of the pro-differentiation factor Bam has been shown to be central in this process. In a Drosophila genetic screen, we discovered that the mutations in Doa, a gene encoding a member of the highly conserved LAMMER/Cdc2-like kinase (CLK) family, cell-autonomously induced the germ cell overproliferation due to the failed transition from mitosis to meiosis. Additional Bam expression in Doa mutant germline promoted the differentiation from the mitotic to the meiotic state. Remarkably, the human or murine CLK2 could prevent the germline overproliferation and even restore the fertility of Doa mutant flies. Such rescuing activity of Doa or its human homolog requires a conserved residue in their predicted kinase catalytic domain. We propose that LAMMER/Cdc2-like kinase, represented by Doa and its mammalian homolog CLK2, is a critical and conserved component in the regulatory program of the mitosis-to-meiosis switch.