Water fluxes through membrane transport proteins

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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?