SACY-1 DEAD-Box helicase links the somatic control of oocyte meiotic maturation to the sperm-to-oocyte switch and gamete maintenance in Caenorhabditis elegans.
SACY-1 DEAD-Box helicase links the somatic control of oocyte meiotic maturation to the sperm-to-oocyte switch and gamete maintenance in Caenorhabditis elegans.
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DOI：
10.1534/genetics.112.143271
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发表时间：
2012-11
期刊：
影响因子：
3.3
通讯作者：
Greenstein D
中科院分区：
文献类型：
--
作者：
Kim S;Govindan JA;Tu ZJ;Greenstein D
在有性生殖的动物中，卵母细胞在双线期或终变期停止，并对激素作出反应而恢复减数分裂（减数分裂成熟）。在秀丽隐杆线虫中，主要的精子蛋白通过涉及体细胞Gα s-腺苷酸环化酶信号传导和体细胞与生殖细胞间隙连接通讯的机制触发减数分裂恢复。利用遗传嵌合体分析，我们表明，Gα s-腺苷酸环化酶信号的主要效应，蛋白激酶A（PKA），是需要在性腺鞘细胞卵母细胞减数分裂成熟和生殖系的减数分裂。这一结果排除了环核苷酸必须通过鞘-卵母细胞间隙连接来激活生殖系中PKA的模型，如在脊椎动物系统中提出的。我们进行了遗传筛选，以确定Gα s-腺苷酸环化酶-PKA信号下游的卵母细胞减数分裂成熟的调节因子。我们从分子水平鉴定了10个调控位点，包括必需和非必需因子。sacy-1编码高度保守的DEAD盒解旋酶，是负调节减数分裂成熟的必需生殖系因子。SACY-1是一种多功能蛋白，它建立了连接减数分裂成熟的体细胞控制与生殖系性别决定和配子维持的机制联系。调节因子包括CoREST样复合物的多个亚基和TWK-1双孔钾通道。这些因子不是减数分裂成熟或其在无精子情况下的负调节所绝对需要的，但累积地起作用以使减数分裂成熟的体细胞控制成为可能。这项工作提供了深入了解的遗传控制减数分裂成熟信号在C。elegans，并且这里鉴定的保守因子可以通过同源性或类比告知其他系统中的分析。
In sexually reproducing animals, oocytes arrest at diplotene or diakinesis and resume meiosis (meiotic maturation) in response to hormones. In Caenorhabditis elegans, major sperm protein triggers meiotic resumption through a mechanism involving somatic Gαs–adenylate cyclase signaling and soma-to-germline gap-junctional communication. Using genetic mosaic analysis, we show that the major effector of Gαs–adenylate cyclase signaling, protein kinase A (PKA), is required in gonadal sheath cells for oocyte meiotic maturation and dispensable in the germ line. This result rules out a model in which cyclic nucleotides must transit through sheath-oocyte gap junctions to activate PKA in the germ line, as proposed in vertebrate systems. We conducted a genetic screen to identify regulators of oocyte meiotic maturation functioning downstream of Gαs–adenylate cyclase–PKA signaling. We molecularly identified 10 regulatory loci, which include essential and nonessential factors. sacy-1, which encodes a highly conserved DEAD-box helicase, is an essential germline factor that negatively regulates meiotic maturation. SACY-1 is a multifunctional protein that establishes a mechanistic link connecting the somatic control of meiotic maturation to germline sex determination and gamete maintenance. Modulatory factors include multiple subunits of a CoREST-like complex and the TWK-1 two-pore potassium channel. These factors are not absolutely required for meiotic maturation or its negative regulation in the absence of sperm, but function cumulatively to enable somatic control of meiotic maturation. This work provides insights into the genetic control of meiotic maturation signaling in C. elegans, and the conserved factors identified here might inform analysis in other systems through either homology or analogy.
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