The calcineurin regulator sra plays an essential role in female meiosis in Drosophila.
Modulatory calcineurin-interacting proteins (MCIPs)--also termed regulators of calcineurin (RCNs), calcipressins, or DSCR1 (Down's syndrome critical region 1)--are highly conserved regulators of calcineurin, a Ca(2+)/calmodulin-dependent protein phosphatase . Although overexpression experiments in several organisms have revealed that MCIPs inhibit calcineurin activity , their in vivo functions remain unclear. Here, we show that the Drosophila MCIP sarah (sra) is essential for meiotic progression in oocytes. Eggs from sra null mothers are arrested at anaphase of meiosis I. This phenotype was due to loss of function of sra specifically in the female germline. Sra is physically associated with the catalytic subunit of calcineurin, and its overexpression suppresses the phenotypes caused by constitutively activated calcineurin, such as rough eye or loss of wing veins. Hyperactivation of calcineurin signaling in the germline cells resulted in a meiotic-arrest phenotype, which can also be suppressed by overexpression of Sra. All these results support the hypothesis that Sra regulates female meiosis by controlling calcineurin activity in the germline. To our knowledge, this is the first unambiguous demonstration that the regulation of calcineurin signaling by MCIPs plays a critical role in a defined biological process.
Takeo
Satomi
S
Department of Biological Sciences, Tokyo Metropolitan University, Hachioji-shi, Japan.
Tsuda
Manabu
M
Akahori
Shin
S
Matsuo
Takashi
T
Aigaki
Toshiro
T
D000705:Anaphase / Q000235:genetics; D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D004330:Drosophila / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000235:genetics; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008540:Meiosis / Q000235:genetics; D009068:Movement / Q000502:physiology; D009154:Mutation; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D010063:Ovum / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D021122:Protein Subunits / Q000378:metabolism; D015398:Signal Transduction
D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D021122:Protein Subunits; C513393:Sra protein, Drosophila; D019703:Calcineurin