Hill A E, Shachar-Hill Y
Physiological Laboratory, Downing Site, Cambridge, CB2 3EG, UK,
J Membr Biol. 2015 Aug;248(4):753-65. doi: 10.1007/s00232-015-9790-0. Epub 2015 Mar 20.
Regulation of cell volume is central to homeostasis. It is assumed to begin with the detection of a change in water potential across the bounding membrane, but it is not clear how this is accomplished. While examples of general osmoreceptors (which sense osmotic pressure in one phase) and stretch-activated ion channels (which require swelling of a cell or organelle) are known, effective volume regulation requires true transmembrane osmosensors (TMOs) which directly detect a water potential difference spanning a membrane. At present, no TMO molecule has been unambiguously identified, and clear evidence for mammalian TMOs is notably lacking. In this paper, we set out a theory of TMOs which requires a water channel spanning the membrane that excludes the major osmotic solutes, responds directly without the need for any other process such as swelling, and signals to other molecules associated with the magnitude of changing osmotic differences. The most likely molecules that are fit for this purpose and which are also ubiquitous in eukaryotic cells are aquaporins (AQPs). We review experimental evidence from several systems which indicates that AQPs are essential elements in regulation and may be functioning as TMOs; i.e. the first step in an osmosensing sequence that signals osmotic imbalance in a cell or organelle. We extend this concept to several systems of current interest in which the cellular involvement of AQPs as simple water channels is puzzling or counter-intuitive. We suggest that, apart from regulatory volume changes in cells, AQPs may also be acting as TMOs in red cells, secretory granules and microorganisms.
细胞体积调节是体内平衡的核心。一般认为它始于对跨边界膜水势变化的检测，但目前尚不清楚这是如何实现的。虽然已知一些一般的渗透压感受器（可感知某一相中的渗透压）和牵张激活离子通道（需要细胞或细胞器肿胀）的例子，但有效的体积调节需要真正的跨膜渗透压感受器（TMO），它能直接检测跨膜的水势差。目前，尚未明确鉴定出任何TMO分子，而且明显缺乏关于哺乳动物TMO的明确证据。在本文中，我们提出了一种TMO理论，该理论认为需要一个跨膜的水通道，它能排除主要的渗透溶质，直接做出反应而无需任何其他过程（如肿胀），并向与渗透压变化幅度相关的其他分子发出信号。最适合此目的且在真核细胞中普遍存在的分子可能是水通道蛋白（AQP）。我们回顾了来自多个系统的实验证据，这些证据表明AQP是调节过程中的关键要素，可能起着TMO的作用；也就是说，它是细胞或细胞器中信号传导渗透压失衡的渗透感受序列的第一步。我们将这一概念扩展到当前几个备受关注的系统，在这些系统中，AQP作为简单水通道的细胞参与情况令人困惑或有违直觉。我们认为，除了细胞中的调节性体积变化外，AQP在红细胞、分泌颗粒和微生物中也可能起着TMO的作用。
