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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Phosphorylation state of a Tob/BTG protein, FOG-3, regulates initiation and maintenance of the Caenorhabditis elegans sperm fate program
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Phosphorylation state of a Tob/BTG protein, FOG-3, regulates initiation and maintenance of the Caenorhabditis elegans sperm fate program

机译：Tob / BTG蛋白FOG-3的磷酸化状态调节秀丽隐杆线虫精子命运程序的启动和维持

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摘要

FOG-3, the single Caenorhabditis elegans Tob/BTG protein, directs germ cells to adopt the sperm fate at the expense of oogenesis. Importantly, FOG-3 activity must be maintained for the continued production of sperm that is typical of the male sex. Vertebrate Tob proteins have antiproliferative activity and ERK phosphorylation of Tob proteins has been proposed to abrogate "antiproliferative" activity. Here we investigate FOG-3 phosphorylation and its effect on sperm fate specification. We found both phosphorylated and unphosphorylated forms of FOG-3 in nematodes. We then interrogated the role of FOG-3 phosphorylation in sperm fate specification. Specifically, we assayed FOG-3 transgenes for rescue of a fog-3 null mutant. Wild-type FOG-3 rescued both initiation and maintenance of sperm fate specification. A FOG-3 mutant with its four consensus ERK phosphorylation sites substituted to ala-nines, called FOG-3(4A), rescued partially: sperm were made transiently but not continuously in both sexes. A different FOG-3 mutant with its sites substituted to glutamates, called FOG-3(4E), had no rescuing activity on its own, but together with FOG-3(4A) rescue was complete. Thus, when FOG-3(4A) and FOG-3(4E) were both introduced into the same animals, sperm fate specification was not only initiated but also maintained, resulting in continuous spermatogenesis in males. Our findings suggest that unphosphorylated FOG-3 initiates the sperm fate program and that phosphorylated FOG-3 maintains that program for continued sperm production typical of males. We discuss implications of our results for Tob/BTG proteins in vertebrates.
机译：单一秀丽隐杆线虫Tob / BTG蛋白FOG-3指导生殖细胞采用精子命运，但会损害卵子的发生。重要的是，必须保持FOG-3活性，才能持续产生男性典型的精子。脊椎动物Tob蛋白具有抗增殖活性，并且有人提出Tob蛋白的ERK磷酸化可消除“抗增殖”活性。在这里我们研究FOG-3磷酸化及其对精子命运规范的影响。我们在线虫中发现了FOG-3的磷酸化和非磷酸化形式。然后，我们询问了FOG-3磷酸化在精子命运规范中的作用。具体来说，我们分析了FOG-3转基因是否有雾3无效突变体的抢救。野生型FOG-3挽救了精子命运规范的建立和维持。一个FOG-3突变体，其四个共有的ERK磷酸化位点被丙氨酸取代，称为FOG-3（4A），部分获救：精子在两性中都是短暂产生的，而不是连续产生的。另一位位点被谷氨酸取代的FOG-3突变体FOG-3（4E）本身没有任何拯救活性，但与FOG-3（4A）一起拯救行动已经完成。因此，当将FOG-3（4A）和FOG-3（4E）都引入同一只动物时，不仅开始了精子命运的确定，而且还维持了它，导致雄性的连续精子发生。我们的发现表明，未磷酸化的FOG-3会启动精子命运程序，而磷酸化的FOG-3会维持该程序以继续男性典型的精子生产。我们讨论了我们的结果对脊椎动物中Tob / BTG蛋白的影响。

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  • 作者

    Myon-Hee Lee; Kyung Won Kim; Clinton T. Morgan; Dyan E. Morgan$; Judith Kimble;

  • 作者单位

    The Howard Hughes Medical Institute, University of Wisconsin, Madison, Wl 53706,Division of Hematology/Oncology, Department of Internal Medicine, Brody School of Medicine at East Carolina University, Greenville, NC 27834;

    Department of Biochemistry, University of Wisconsin, Madison, Wl 53706;

    Department of Biochemistry, University of Wisconsin, Madison, Wl 53706;

    Program in Cellular and Molecular Biology, University of Wisconsin, Madison, Wl 53706;

    The Howard Hughes Medical Institute, University of Wisconsin, Madison, Wl 53706,Department of Biochemistry, University of Wisconsin, Madison, Wl 53706,Program in Cellular and Molecular Biology, University of Wisconsin, Madison, Wl 53706;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    sex determination; sperm/oocyte decision; germline;

    机译：性别决定;精子/卵母细胞决定;生殖细胞;

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