Water fluxes through membrane transport proteins

通过膜转运蛋白的水通量

• 批准号: 380738-2010
• 负责人: Lapointe, JeanYves
• 金额: $ 4.44万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528626
• 关键词: Water; fluxes; through; membrane; transport

Every biological cell is surrounded by a lipid membrane containing a variety of proteins that allow the cell to maintain a stable intracellular content while being able to communicate with the exterior world. It is clear that this membrane needs to be water permeable for several reasons including cell growth. In the 1950's, it was progressively realised that, on top of water diffusion through the lipid bilayer, a significant fraction of the water movement was going through membrane proteins. One of these membrane proteins was finally identified in 1992 and named "aquaporin" by Peter Agree who won the Nobel Prize of chemistry in 2003 for this discovery. Interestingly, other types of membrane proteins which are used to mediate glucose transport were also found to be water permeable but this aspect of their properties has not been studied in details. The present research program is aimed at understanding the role played by the water permeability of different transport proteins. On the one hand, it is possible that transport proteins contribute significantly to the macroscopic membrane water permeability. On the other hand, it is also possible that the presence of a water flux through a transport protein is aimed at increasing the efficiency of solute transport. In the next 5 years, we would like to answer 4 general questions concerning this problem. #1) What is the physiological importance of transporter-mediated water fluxes? We plan to investigate more than 20 different transport proteins expressed in oocytes. We will also study native membrane using brush border membrane vesicles from kidney and intestine as well as several cell lines. #2) What is the biophysical properties of the water permeation pathway? Using a variety of small solute molecules, we will estimate the size of the water pathway. #3) What is the molecular pathway used by water to cross the Na/glucose cotransporter (SGLT1)? The crystal structure of vSGLT (a bacterial homologue of SGLT1) will be used to identify a series of sites that could accept water molecules and, together, constitute a water pathway. Finally, #4) how does the presence of a water flow through a given transporter affect its function?

每个生物细胞都被一层含有各种蛋白质的脂膜所包围，这些蛋白质使细胞在与外部世界沟通的同时保持稳定的细胞内内容物。很明显，由于包括细胞生长在内的几个原因，这种膜需要具有透水性。在20世纪50年代，S逐渐认识到，在水通过脂双层扩散的基础上，很大一部分水的运动是通过膜蛋白。其中一种膜蛋白最终在1992年被发现，并被2003年诺贝尔化学奖得主彼得·雅格特命名为“水通道蛋白”。有趣的是，用于介导葡萄糖转运的其他类型的膜蛋白也被发现是透水性的，但这方面的性质还没有得到详细的研究。目前的研究计划旨在了解不同运输蛋白的透水性所起的作用。一方面，转运蛋白可能对宏观膜透性有重要贡献。另一方面，也有可能通过运输蛋白存在水通量的目的是为了提高溶质运输的效率。在接下来的5年里，我们想回答关于这个问题的4个一般性问题。#1)转运体介导的水通量的生理重要性是什么？我们计划研究在卵母细胞中表达的20多种不同的转运蛋白。我们还将使用来自肾和肠以及几个细胞系的刷状边缘膜囊来研究天然膜。#2)水渗透途径的生物物理特性是什么？使用各种小的溶质分子，我们将估计水路径的大小。#3)水通过钠/葡萄糖共转运体(SGLT1)的分子途径是什么？VSGLT(SGLT1的细菌同源物)的晶体结构将被用来识别一系列可以接受水分子的位置，并共同构成一条水途径。最后，#4)流经特定传输器的水流对其功能有何影响？