Shaggy/glycogen synthase kinase 3β and phosphorylation of Sarah/regulator of calcineurin are essential for completion of Drosophila female meiosis

被引:36
作者
Takeo, Satomi [1 ]
Swanson, Selene K. [1 ]
Nandanan, Kavyasree [1 ]
Nakai, Yasuhiro [2 ]
Aigaki, Toshiro [2 ]
Washburn, Michael P. [1 ,3 ]
Florens, Laurence [1 ]
Hawley, R. Scott [1 ,4 ]
机构
[1] Stowers Inst Med Res, Kansas City, MO 64110 USA
[2] Tokyo Metropolitan Univ, Dept Biol Sci, Hachioji, Tokyo 1920397, Japan
[3] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA
[4] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA
基金
日本学术振兴会;
关键词
EGG ACTIVATION; MELANOGASTER; IDENTIFICATION; REGULATORS; INHIBITOR; PROTEINS; TRIGGERS; FAMILY; YEAST; RCAN;
D O I
10.1073/pnas.1120367109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Ca2+/Calmodulin-dependent phosphatase calcineurin is essential for exit from meiotic arrest at metaphases I and II in Drosophila and Xenopus oocytes. We previously found that Sarah, the Drosophila homolog of regulator of calcineurin, acts as a positive regulator of calcineurin and is required to complete anaphase I of female meiosis. Here, we undertook biochemical approaches, including MS and posttranslational modification analyses, to better understand the mechanism by which Sarah regulates calcineurin. A search for phosphorylated residues revealed that Sarah is highly phosphorylated at Ser100, Thr102, and Ser219 in both ovaries and activated eggs and that Ser215 is phosphorylated only in activated eggs. Functional analyses using mutant forms of Sarah showed that phosphorylation at Ser215, a consensus phosphorylation site for glycogen synthase kinase 3 beta (GSK-3 beta)and its priming kinase site Ser219, are essential for Sarah function. Furthermore, germ-line clones homozygous for a null allele of shaggy ( Drosophila GSK-3 beta) both fail to complete meiosis and lack phosphorylation of Sarah at Ser215, suggesting that the phosphorylation of Sarah by Shaggy/GSK-3 beta is required to complete meiosis. Our findings suggest a mechanism in which Shaggy/GSK-3 beta activates calcineurin through Sarah phosphorylation on egg activation in Drosophila.
引用
收藏
页码:6382 / 6389
页数:8
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