Knapp Elizabeth, Sun Jianjun
Department of Physiology & Neurobiology, University of Connecticut, Storrs, CT 06269.
Department of Physiology & Neurobiology, University of Connecticut, Storrs, CT 06269;
Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):699-704. doi: 10.1073/pnas.1614383114. Epub 2017 Jan 9.
Although ecdysteroid signaling regulates multiple steps in oogenesis, it is not known whether it regulates Drosophila ovulation, a process involving a matrix metalloproteinase-dependent follicle rupture. In this study, we demonstrated that ecdysteroid signaling is operating in mature follicle cells to control ovulation. Moreover, knocking down shade (shd), encoding the monooxygenase that converts ecdysone (E) to the more active 20-hydroxyecdysone (20E), specifically in mature follicle cells, blocked follicle rupture, which was rescued by ectopic expression of shd or exogenous 20E. In addition, disruption of the Ecdysone receptor (EcR) in mature follicle cells mimicked shd-knockdown defects, which were reversed by ectopic expression of EcR.B2 but not by EcR.A or EcR.B1 isoforms. Furthermore, we showed that ecdysteroid signaling is essential for the proper activation of matrix metalloproteinase 2 (Mmp2) for follicle rupture. Our data strongly suggest that 20E produced in follicle cells before ovulation activates EcR.B2 to prime mature follicles to be responsive to neuronal ovulatory stimuli, thus providing mechanistic insights into steroid signaling in Drosophila ovulation.
尽管蜕皮甾体信号传导调节卵子发生的多个步骤，但尚不清楚它是否调节果蝇排卵，这一过程涉及基质金属蛋白酶依赖性的卵泡破裂。在本研究中，我们证明蜕皮甾体信号传导在成熟卵泡细胞中起作用以控制排卵。此外，特异性地在成熟卵泡细胞中敲低编码将蜕皮酮（E）转化为活性更高的20-羟基蜕皮酮（20E）的单加氧酶的遮光蛋白（shd），会阻断卵泡破裂，而shd的异位表达或外源性20E可挽救这种阻断。另外，成熟卵泡细胞中蜕皮激素受体（EcR）的破坏模拟了shd敲低的缺陷，EcR.B2的异位表达可逆转这些缺陷，而EcR.A或EcR.B1亚型则不能。此外，我们表明蜕皮甾体信号传导对于基质金属蛋白酶2（Mmp2）的适当激活以实现卵泡破裂至关重要。我们的数据强烈表明，排卵前卵泡细胞中产生的20E激活EcR.B2，使成熟卵泡对神经元排卵刺激作出反应，从而为果蝇排卵中的甾体信号传导提供了机制上的见解。
