Rapid aquaporin translocation regulates cellular water flow: mechanism of hypotonicity-induced subcellular localization of aquaporin 1 water channel.
Rapid aquaporin translocation regulates cellular water flow: mechanism of hypotonicity-induced subcellular localization of aquaporin 1 water channel.
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DOI：
10.1074/jbc.m111.329219
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发表时间：
2012-03-30
期刊：
影响因子：
--
通讯作者：
Bill RM
中科院分区：
文献类型：
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作者：
Conner MT;Conner AC;Bland CE;Taylor LH;Brown JE;Parri HR;Bill RM
背景：水通道蛋白通道确保所有细胞中适当的膜透水性。结果如下：在低渗刺激后，水通道蛋白1的亚细胞定位通过依赖于瞬时受体电位通道、细胞外钙内流、钙调蛋白和水通道蛋白1的两个苏氨酸（157和239）的磷酸化的机制发生。结论：水通道蛋白1的快速转位调节细胞膜透性。意义：该机制可能作为水通道蛋白功能快速调节的原型。细胞水流动的控制是由水通道蛋白（AQP）家族的膜蛋白介导的。该家族的结构特征和通过AQP孔的选择性水通道的机制已经建立，但在我们对水运输如何调节的知识中仍然存在空白。有两种可能性。一个是控制水通过AQP孔，但这只是在一些植物和微生物AQP中观察到的现象。另一种方法是控制细胞膜中AQP的数量。在这里，我们描述了一种新的途径，在哺乳动物细胞中，低渗刺激直接诱导细胞内钙离子升高，通过瞬时受体电位通道，触发AQP1易位。这种在细胞体积调节中具有直接作用的易位在30 s内发生，并且依赖于钙调蛋白激活和蛋白激酶C在两个苏氨酸残基处对AQP1的磷酸化。这种直接机制为水运输的变化提供了理论依据，而这种变化是为了应对不断变化的当地细胞水供应。此外，由于钙是生物系统中的多能性和普遍存在的第二信使，其在调节AQP易位中的作用的发现对于不同的生理和病理生理过程具有分支，并且为细胞稳态所必需的水流的快速调节提供了解释。
Background: Aquaporin channels ensure appropriate membrane permeability to water in all cells. Results: Following a hypotonic stimulus, subcellular localization of aquaporin 1 occurs via a mechanism dependent on transient receptor potential channels, extracellular calcium influx, calmodulin, and the phosphorylation of two threonines (157 and 239) of aquaporin 1. Conclusion: Rapid translocation of aquaporin 1 regulates membrane water permeability. Significance: This mechanism may serve as a prototype for the rapid regulation of aquaporin function. The control of cellular water flow is mediated by the aquaporin (AQP) family of membrane proteins. The structural features of the family and the mechanism of selective water passage through the AQP pore are established, but there remains a gap in our knowledge of how water transport is regulated. Two broad possibilities exist. One is controlling the passage of water through the AQP pore, but this only has been observed as a phenomenon in some plant and microbial AQPs. An alternative is controlling the number of AQPs in the cell membrane. Here, we describe a novel pathway in mammalian cells whereby a hypotonic stimulus directly induces intracellular calcium elevations through transient receptor potential channels, which trigger AQP1 translocation. This translocation, which has a direct role in cell volume regulation, occurs within 30 s and is dependent on calmodulin activation and phosphorylation of AQP1 at two threonine residues by protein kinase C. This direct mechanism provides a rationale for the changes in water transport that are required in response to constantly changing local cellular water availability. Moreover, because calcium is a pluripotent and ubiquitous second messenger in biological systems, the discovery of its role in the regulation of AQP translocation has ramifications for diverse physiological and pathophysiological processes, as well as providing an explanation for the rapid regulation of water flow that is necessary for cell homeostasis.