Human AQP1 Is a Constitutively Open Channel that Closes by a Membrane-Tension-Mediated Mechanism

Abstract

This work presents experimental results combined with model-dependent predictions regarding the osmotic-permeability regulation of human aquaporin 1 (hAQP1) expressed in Xenopus oocyte membranes. Membrane elastic properties were studied under fully controlled conditions to obtain a function that relates internal volume and pressure. This function was used to design a model in which osmotic permeability could be studied as a pressure-dependent variable. The model states that hAQP1 closes with membrane-tension increments. It is important to emphasize that the only parameter of the model is the initial osmotic permeability coefficient, which was obtained by model-dependent fitting. The model was contrasted with experimental records from emptied-out Xenopus laevis oocytes expressing hAQP1. Simulated results reproduce and predict volume changes in high-water-permeability membranes under hypoosmotic gradients of different magnitude, as well as under consecutive hypo- and hyperosmotic conditions. In all cases, the simulated permeability coefficients are similar to experimental values. Predicted pressure, volume, and permeability changes indicate that hAQP1 water channels can transit from a high-water-permeability state to a closed state. This behavior is reversible and occurs in a cooperative manner among monomers. We conclude that hAQP1 is a constitutively open channel that closes mediated by membrane-tension increments.

Aquaporins: important but elusive drug targets

“…This finding adds to the knowledge of the structural basis of AQP gating 17 ; previous experimentally and computationally derived mechanisms proposed that AQP gating involved mechanosensitivity and phosphorylation in yeast AQPs 18 , and membrane tension in both mammalian and yeast AQPs 19–21 .…”

Aquaporins: Highly Regulated Channels Controlling Plant Water Relations

“…oocytes, but this effect was also observed on water-injected oocytes (Wei et al, 2007). Some evidence supports also the direct role of aquaporins as osmo-or pressure sensors (MacRobbie, 2006;Ozu et al, 2013;Shachar-Hill et al, 2013), as was proposed earlier (Hill et al, 2004). However, there is also ample evidence for the presence and functioning of mechanosensitive ion channels in plant membranes that could transduce pressure signals and affect aquaporins via second messenger systems (Monshausen and Haswell, 2013).…”

“…However, isolated membrane vesicles can also show aquaporin-mediated water permeability that is highly dependent on osmotic pressure (Vandeleur et al, 2005). Recently, it has been shown that human AQP1 is constitutively open but closes with increases in membrane tension (Ozu et al, 2013).…”

Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress

“…Furthermore, gating mechanisms that induce a change in the 3D-channel structure and consequently affect its transport activity [2] have been described for several eukaryotic AQPs [21,22,23,24], among which pH and phosphorylation represent a short-term regulatory mechanism commonly used by several AQP family members [24,25]. However, besides its post-translational modification by phosphorylation, gating mechanisms for AQP5 channel activity regulation have not been reported so far.…”