Aquaporin Gating: A New Twist to Unravel Permeation through Water Channels

Abstract

Aquaporins (AQPs) are small transmembrane tetrameric proteins that facilitate water, solute and gas exchange. Their presence has been extensively reported in the biological membranes of almost all living organisms. Although their discovery is much more recent than ion transport systems, different biophysical approaches have contributed to confirm that permeation through each monomer is consistent with closed and open states, introducing the term gating mechanism into the field. The study of AQPs in their native membrane or overexpressed in heterologous systems have experimentally demonstrated that water membrane permeability can be reversibly modified in response to specific modulators. For some regulation mechanisms, such as pH changes, evidence for gating is also supported by high-resolution structures of the water channel in different configurations as well as molecular dynamics simulation. Both experimental and simulation approaches sustain that the rearrangement of conserved residues contributes to occlude the cavity of the channel restricting water permeation. Interestingly, specific charged and conserved residues are present in the environment of the pore and, thus, the tetrameric structure can be subjected to alter the positions of these charges to sustain gating. Thus, is it possible to explore whether the displacement of these charges (gating current) leads to conformational changes? To our knowledge, this question has not yet been addressed at all. In this review, we intend to analyze the suitability of this proposal for the first time.

Functional regulation of aquaporin dynamics by lipid bilayer composition

“…Loop A, and its homologous sequences in non-PIP orthodox AQPs, typically engage in direct hydrogen bonding contacts and/or disulfide bridges to help with monomer association and tetramer assembly 27 . AQP proteins are ubiquitously found as tetramers, but each monomer constitutes a functionally independent pore 28 . We used SoPIP2;1 monomers to complete this study due to the computational efficiency and literature-based justification (see “Methods—System assembly”).…”

“…Lateral exchange of annular shell lipids with the bulk has therefore been suggested as a regulatory mechanism for AQP function 39 . Conserved channel residue rearrangements have also been posited as a regulatory means to affect AQP water transport 28 , 39 . Perhaps lipid binding itself could be the fundamental driver of either proposed regulatory mechanism.…”

“…The computational efficiency associated with the use of monomer SoPIP2;1 is further justified by experimental findings and related literature reviews. AQP monomers are known to constitute functionally independent pores 28 . Each AQP monomer can be functionally reconstituted in vitro 78 , 79 , and even functional AQP monomer structures have been resolved by solid state NMR spectroscopy (PDB IDs: 8H1D and 6POJ) 80 , 81 .…”

Real-Time Dynamics of Water Transport in the Roots of Intact Maize Plants in Response to Water Stress: The Role of Aquaporins and the Contribution of Different Water Transport Pathways

“…Rapid changes in cell membrane permeability are thought to be associated with the opening/closure of AQPs as a result of changes in their conformation. This mechanism, known as AQP gating, can be realized by chemical, mechanical, and even electrical stimuli [45,46]. Vandeleur et al's work on shoot-to-root signaling showed that leaf cutting in soybean and maize plants caused rapid, within a few minutes, changes in turgor pressure and membrane permeability in the root cells [47].…”

“…For example, Liang Fang and co-authors showed that changes in the stomatal conductance, root and leaf hydraulic conductance, and AQP gene expression in tomato plant roots under increasing atmospheric CO2 concentration were accompanied by changes in the xylem sap pH [61]. The change in pH can both act as an activator of hydrogen peroxide synthesis and directly affect the activity of AQPs via phosphorylation [45]. Thus, the change in xylem sap pH under water stress can be an additional regulatory factor.…”