Aquaporins

Since biological membranes have only limited water permeability cells assist the flow of water into and out of the cell using water-specific membrane protein channels called aquaporins. The discovery of these water channels earned Peter Agre the Nobel Prize in Chemistry for 2003. These water channels are found throughout all kingdoms of life (eg. bacteria, yeast, animals & plants). In humans the aquaporins are implicated in cancer, brain edema, cardiovascular complications, diabetes & many other serious conditions. 

Throughout the year plants are exposed to a variety of local environmental conditions. They have evolved to cope with rapid changes in the availability of water by regulating all plasma membrane aquaporins (Fig. 1), which lie directly inside of the plant cell wall. Under conditions of drought stress these plant aquaporins are closed so as to slow down the loss of water and enable other protective biochemical pathways to be switched on. As such the loss of turgor pressure, which keeps plant cells bouyant & gives plants their rigid structure, can be delayed during water shortage. Curiously, the same aquaporins also close in response to flooding, although the exact physiological reason for this remains speculative.

Schematic illustration of how plant plasma membrane aquaporins are gated. Under normal conditions the aquaporin is phosphorylated (indicated by P) & the water channel is open. During drought stress these aquaporins close in response to the removal of phosphate groups from two conserved serine residues. During flooding the aquaporins close in response to the protonation of a conserved histidine (indicated by H+).

In collaboration with academic groups in Lund (Sweden) & Urbana (USA) we have determined the x-ray structure of a gated spinach plasma membrane aquaporin in both its open & closed conformations, & have performed molecular dynamics simulations of the initial gating events. Through this work a structural mechanism explaining how plant plasma membrane aquaporins are opened & closed was revealed, unifying an otherwise puzzling body of biochemical evidence. As illustrated below, in the closed conformation a flexible loop caps the channel from the inside of the cell & Leu197 thereby occludes the access of water into the pore. In the open conformation this loop is displaced up to 16 Å & this movement opens a hydrophobic gate blocking the channel entrance from the cytoplasm.

X-ray structure of the open & closed forms of the gated spinach aquaporin SoPIP2;1. Eight water molecules (red spheres) are seen to line up along the water transport channel & the grey dotted tube represents the diameter of the water-channel. In the open conformation (right) there is space for water molecules to move through the entire length of the pore, whereas in the closed conformation (left) the aquaporin is blocked from the inside of the cell (bottom).

These structural results provide a deeper understanding of the how the flow of water is regulated within all land plants on earth, & is thus applicable to phenomena as every-day as a neglected pot-plant wilting or the flood irrigation of the rice paddies of Asia. Furthermore, several of the human aquaporins are regulated (gated or traffiked into different membranes) by pH, phosphorylation or the binding of cations. As such structural results from plant aquaporins may also aid the understanding of the complex systems of water regulation within the human body.