Calcineurin-mediated Dephosphorylation of Acetyl-coA Carboxylase is Required for Pheromone Biosynthesis Activating Neuropeptide (PBAN)-induced Sex Pheromone Biosynthesis in Helicoverpa armigera
Calcineurin-mediated Dephosphorylation of Acetyl-coA Carboxylase is Required for Pheromone Biosynthesis Activating Neuropeptide (PBAN)-induced Sex Pheromone Biosynthesis in Helicoverpa armigera
复制标题
棉铃虫信息素生物合成激活神经肽 (PBAN) 诱导的性信息素生物合成需要钙调神经磷酸酶介导的乙酰辅酶 A 羧化酶去磷酸化
DOI：
10.1074/mcp.ra117.000065
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发表时间：
2017-12-01
影响因子：
7
通讯作者：
An, Shiheng
中科院分区：
文献类型：
--
作者：
Du, Mengfang;Liu, Xiaoguang;An, Shiheng
化学信号在许多动物的行为和生理中起着关键作用。雌性昆虫和许多其他动物一样，释放性信息素吸引雄性交配。因此，昆虫的进化和生态成功取决于它们精确介导（包括起始和终止）信息素生物合成的能力。信息素生物合成激活神经肽（PBAN）在大多数物种中直接作用于信息素腺体，以Ca ~（2+）和环腺苷酸（cyclic-AMP）作为第二信使调节性信息素的产生。然而，次级信使下游的分子机制尚未阐明在太阳神物种。本研究利用PBAN依赖的磷酸化蛋白质组学结合转录组学技术，发现钙调磷酸酶、蛋白激酶A（PKA）和乙酰辅酶A羧化酶（ACC）是参与PBAN诱导的棉铃虫性信息素生物合成的关键组分。RNAi介导的敲除和抑制剂测定表明，钙调磷酸酶A是PBAN诱导的ACC激活和性信息素产生所必需的。钙调神经磷酸酶依赖的磷酸化蛋白质组学和体外钙调神经磷酸酶磷酸化分析进一步揭示了钙调神经磷酸酶通过去磷酸化ser 84和ser 92来调节ACC活性。此外，PKA依赖的磷酸化蛋白质组学和活性分析表明，PKA降低AMP活化蛋白激酶（AMPK）的活性，AMPK是ACC的负调节因子，通过磷酸化保守的ser 92。总而言之，我们的研究结果表明钙调神经磷酸酶作为PBAN/G蛋白受体/Ca 2+的下游信号，通过去磷酸化激活ACC，同时通过PKA灭活AMPK，减少ACC磷酸化，从而促进钙调神经磷酸酶激活ACC。
Chemical signaling plays a critical role in the behavior and physiology of many animals. Female insects, as many other animals, release sex pheromones to attract males for mating. The evolutionary and ecological success of insects therefore hinges on their ability to precisely mediate (including initiation and termination) pheromone biosynthesis. Pheromone biosynthesis activating neuropeptide (PBAN) acts directly on pheromone glands to regulate sex pheromone production using Ca2+ and cyclic-AMP as secondary messengers in the majority of species. However, the molecular mechanism downstream of the secondary messengers has not yet been elucidated in heliothine species. The present study shows that calcineurin, protein kinase A (PKA) and acetyl-coA carboxylase (ACC) are key components involved in PBAN-induced sex pheromone biosynthesis in Helicoverpa armigera using PBAN-dependent phosphoproteomics in combination with transcriptomics. RNAi-mediated knockdown and inhibitor assay demonstrated that calcineurin A is required for PBAN-induced ACC activation and sex pheromone production. Calcineurin-dependent phosphoproteomics and in vitro calcineurin phosphorylation assay further revealed that calcineurin regulated ACC activity by dephosphorylating ser84 and ser92. In addition, PKA-dependent phosphoproteomics and activity analysis revealed that PKA reduces the activity of AMP-activated protein kinase (AMPK), a negative regulator of ACC by phosphorylating the conserved ser92. Taken together, our findings indicate that calcineurin acts as the downstream signal of PBAN/G-protein receptor/Ca2+ to activate ACC through dephosphorylation while inactivating AMPK via PKA to reduce ACC phosphorylation, thus facilitating calcineurin activation of ACC.