Fundamental structural and functional properties of Aquaporin ion channels found across the kingdoms of life

Abstract

Aquaporin (AQP) channels in the major intrinsic protein (MIP) family are known to facilitate transmembrane water fluxes in prokaryotes and eukaryotes. Some classes of AQPs also conduct ions, glycerol, urea, CO , nitric oxide, and other small solutes. Ion channel activity has been demonstrated for mammalian AQPs 0, 1, 6, Drosophila Big Brain (BIB), soybean nodulin 26, and rockcress AtPIP2;1. More classes are likely to be discovered. Newly identified blockers are providing essential tools for establishing physiological roles of some of the AQP dual water and ion channels. For example, the arylsulfonamide AqB011 which selectively blocks the central ion pore of mammalian AQP1 has been shown to impair migration of HT29 colon cancer cells. Traditional herbal medicines are sources of selective AQP1 inhibitors that also slow cancer cell migration. The finding that plant AtPIP2;1 expressed in root epidermal cells mediates an ion conductance regulated by calcium and protons provided insight into molecular mechanisms of environmental stress responses. Expression of lens MIP (AQP0) is essential for maintaining the structure, integrity and transparency of the lens, and Drosophila BIB contributes to neurogenic signalling pathways to control the developmental fate of fly neuroblast cells; however, the ion channel roles remain to be defined for MIP and BIB. A broader portfolio of pharmacological agents is needed to investigate diverse AQP ion channel functions in situ. Understanding the dual water and ion channel roles of AQPs could inform the development of novel agents for rational interventions in diverse challenges from agriculture to human health.

Phosphorylation influences water and ion channel function of AtPIP2;1

“…The central pore, formed in the middle of the four monomeric channels, has been proposed to be the exclusive channel for ion transport through the AtPIP2;1 homotetramer (Kourghi et al, 2018). The phosphorylation state of the CTD is known to be involved in gating of water transport through the monomeric pores, via reinforcing specific steric forms of the cytoplasmic facing loops and protein termini (Frick et al, 2013; Nyblom et al, 2009; Törnroth‐Horsefield et al, 2006).…”

“…The full‐length cDNA of AtPIP2;1 and AtPIP2;1 single‐ and double‐point C‐terminal phosphorylation mutations (Table S1) generated in gateway enabled entry vectors were subcloned into pYES‐DEST 52 (Invitrogen) yeast expression destination vector driven by GAL1 promoter through LR reaction. Empty vector and AtPIP2;7 (following Kourghi et al, 2018) were also included as negative controls. Confirmed constructs were transformed into S. cerevisiae strain B31 ( Δena1::HIS3::ena4 , Δnha1::LEU2 ) (Banuelos, Sychrova, Bleykasten‐Grosshans, Souciet, & Potier, 1998) using Frozen‐EZ Yeast Transformation II kit (Zymo Research).…”

Xylem Ion Loading and Its Implications for Plant Abiotic Stress Tolerance

“…Water permeability through AtPIP2;1 is also regulated by phosphorylation (Prado et al, 2013), but the regulation of its ionic conductance (including Na + ) is not yet clear. Due to similar cyclic nucleotide signalling cascades present in animal and plant cells (Isner, Nühse, & Maathuis, 2012;Maurel et al, 1995), the mechanism known to control ion and water transport in mammalian AQP1 (including phosphorylation) should also be explored in AtPIP2;1 (reviewed by Kourghi et al, 2018). In plants, the level of cGMP is increased by ABA perception (Isner et al, 2012), and ABA modulates aquaporin conductance in response to water stress (Parent et al, 2009).…”

Identification of Loop D Domain Amino Acids in the Human Aquaporin-1 Channel Involved in Activation of the Ionic Conductance and Inhibition by AqB011

“…Aquaporin channels are more than simple pathways for the passive flux of water and glycerol. As a group they are increasingly being found to include highly specialized, regulated, multifunctional channels with diverse roles across the kingdoms of life (Gomes et al, 2009 ; Kourghi et al, 2017a ). Results here contribute to understanding the structural basis for gating and pharmacological block of the human AQP1 ion channel, and add further evidence supporting the role of the central pore as the pathway for ion flux in human AQP1.…”