Encystation stimuli sensing is mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia.
Encystation stimuli sensing is mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia.
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DOI：
10.1038/s41467-023-43028-1
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发表时间：
2023-11-09
影响因子：
16.6
通讯作者：
Paredez, Alexander R
中科院分区：
文献类型：
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作者：
Shih, Han-Wei;Alas, Germain C M;Paredez, Alexander R
原生动物寄生虫使用cAMP信号来精确调节发育分化的地点和时间，但目前尚不清楚这种信号是如何启动的。肠道寄生虫贾第鞭毛虫的寄生可以被多种刺激激活，我们假设这导致了一种共同的生理变化。我们证明胆汁通过减少富含胆固醇的脂质微域改变质膜流动性，而碱性pH增强胆汁功能。通过去除产生cAMP的腺苷酸环化酶2 （Adenylate Cyclase 2, AC2）和使用新开发的贾第虫特异性cAMP传感器，我们发现AC2对于环胞刺激诱导的cAMP升高和下游信号的激活是必需的。相反，过表达AC2或外源性cAMP足以启动胞囊。我们的研究结果表明，囊化刺激诱导膜重组，触发ac2依赖性cAMP上调，并启动囊化特异性基因表达，从而促进了我们对全球重要寄生虫生命周期关键阶段的理解。贾第鞭毛虫是一种已经建立的研究细菌感染的模型。Shih等人的研究表明，胆汁和碱性pH可诱导膜的有序变化，上调cAMP，并启动encystation基因的表达。
Protozoan parasites use cAMP signaling to precisely regulate the place and time of developmental differentiation, yet it is unclear how this signaling is initiated. Encystation of the intestinal parasite Giardia lamblia can be activated by multiple stimuli, which we hypothesize result in a common physiological change. We demonstrate that bile alters plasma membrane fluidity by reducing cholesterol-rich lipid microdomains, while alkaline pH enhances bile function. Through depletion of the cAMP producing enzyme Adenylate Cyclase 2 (AC2) and the use of a newly developed Giardia-specific cAMP sensor, we show that AC2 is necessary for encystation stimuli-induced cAMP upregulation and activation of downstream signaling. Conversely, over expression of AC2 or exogenous cAMP were sufficient to initiate encystation. Our findings indicate that encystation stimuli induce membrane reorganization, trigger AC2-dependent cAMP upregulation, and initiate encystation-specific gene expression, thereby advancing our understanding of a critical stage in the life cycle of a globally important parasite. Giardia lamblia is an established model for studying encystation. Shih et al show bile and alkaline pH induce changes in membrane ordering, upregulate cAMP, and initiate encystation gene expression.