Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules
Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules
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DOI：
10.1016/j.ijpara.2015.12.001
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发表时间：
2016-06-01
影响因子：
4
通讯作者：
Walker, Anthony J.
中科院分区：
文献类型：
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作者：
Hirst, Natasha L.;Lawton, Scott P.;Walker, Anthony J.
环磷酸腺苷 (cAMP) 依赖性蛋白激酶/蛋白激酶 A 通过磷酸化多种细胞底物（包括代谢和信号酶、离子通道和转录因子）来调节真核生物中的多个过程。在这里，我们深入了解尾蚴和 24 小时体外培养的血液寄生虫曼氏血吸虫（引起人类肠道血吸虫病）的体细胞中的蛋白激酶 A 信号传导。使用抗磷酸蛋白激酶 A 抗体和共聚焦激光扫描显微镜对活化蛋白激酶 A 进行功能图谱显示，中枢和周围神经系统、口尖感觉乳头、食道和完整尾蚴的排泄系统中存在活化蛋白激酶 A。培养的 24 小时体细胞在生物学上代表了寄生虫的皮肤驻留阶段，在食道和神经组织中表现出类似的激活模式，但在皮层和类似于生发“干”细胞簇的区域也显示出惊人的激活。腺苷酸环化酶激活剂毛喉素刺激 somule 蛋白激酶 A 激活并产生运动机能亢进表型。已知存在于皮肤中的生物胺、血清素和多巴胺也会诱导体细胞中蛋白激酶 A 的激活，而神经肽 Y 或 [Leu(31),Pro(34)]-神经肽 Y 会减弱蛋白激酶 A 的激活。然而，神经肽 Y 并不能阻断毛喉素诱导的体运动亢进。对潜在蛋白质关联的生物信息学研究揭示了曼氏沙门氏菌中 193 个中等可信度和 59 个高可信度的蛋白激酶 A 相互作用伙伴，其中许多具有推定的蛋白激酶 A 磷酸化位点。这些数据为了解曼氏血吸虫中蛋白激酶 A 信号传导的复杂性提供了宝贵的见解，并为进一步研究蛋白激酶 A 在血吸虫中的作用（特别是在寄生虫与宿主之间的相互作用的背景下）的生理学研究提供了框架。 (C) 2016 年澳大利亚寄生虫学会。由爱思唯尔有限公司出版。保留所有权利。
Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A regulates multiple processes in eukaryotes by phosphorylating diverse cellular substrates, including metabolic and signalling enzymes, ion channels and transcription factors. Here we provide insight into protein kinase A signalling in cercariae and 24 h in vitro cultured somules of the blood parasite, Schistosoma mansoni, which causes human intestinal schistosomiasis. Functional mapping of activated protein kinase A using anti-phospho protein kinase A antibodies and confocal laser scanning microscopy revealed activated protein kinase A in the central and peripheral nervous system, oral-tip sensory papillae, oesophagus and excretory system of intact cercariae. Cultured 24 h somules, which biologically represent the skin-resident stage of the parasite, exhibited similar activation patterns in oesophageal and nerve tissues but also displayed striking activation at the tegument and activation in a region resembling the germinal 'stem' cell cluster. The adenylyl cyclase activator, forskolin, stimulated somule protein kinase A activation and produced a hyperkinesia phenotype. The biogenic amines, serotonin and dopamine known to be present in skin also induced protein kinase A activation in somules, whereas neuropeptide Y or [Leu(31),Pro(34)]-neuropeptide Y attenuated protein kinase A activation. However, neuropeptide Y did not block the forskolin-induced somule hyperkinesia. Bioinformatic investigation of potential protein associations revealed 193 medium confidence and 59 high confidence protein kinase A interacting partners in S. mansoni, many of which possess putative protein kinase A phosphorylation sites. These data provide valuable insight into the intricacies of protein kinase A signalling in S. mansoni and a framework for further physiological investigations into the roles of protein kinase A in schistosomes, particularly in the context of interactions between the parasite and the host. (C) 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.