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International Journal of Molecular... Oct 2017Aquaporins are tetrameric membrane-bound channels that facilitate transport of water and other small solutes across cell membranes. In eukaryotes, they are frequently... (Review)
Review
Aquaporins are tetrameric membrane-bound channels that facilitate transport of water and other small solutes across cell membranes. In eukaryotes, they are frequently regulated by gating or trafficking, allowing for the cell to control membrane permeability in a specific manner. Protein-protein interactions play crucial roles in both regulatory processes and also mediate alternative functions such as cell adhesion. In this review, we summarize recent knowledge about aquaporin protein-protein interactions; dividing the interactions into three types: (1) interactions between aquaporin tetramers; (2) interactions between aquaporin monomers within a tetramer (hetero-tetramerization); and (3) transient interactions with regulatory proteins. We particularly focus on the structural aspects of the interactions, discussing the small differences within a conserved overall fold that allow for aquaporins to be differentially regulated in an organism-, tissue- and trigger-specific manner. A deep knowledge about these differences is needed to fully understand aquaporin function and regulation in many physiological processes, and may enable design of compounds targeting specific aquaporins for treatment of human disease.
Topics: Animals; Aquaporins; Carrier Proteins; Cell Membrane Permeability; Humans; Ion Channel Gating; Phosphorylation; Protein Binding; Protein Interaction Domains and Motifs; Protein Multimerization; Signal Transduction; Structure-Activity Relationship
PubMed: 29077056
DOI: 10.3390/ijms18112255 -
Biochimica Et Biophysica Acta.... Sep 2021Aquaporin water channels facilitate the bi-directional flow of water and small, neutral solutes down an osmotic gradient in all kingdoms of life. Over the last two... (Review)
Review
Aquaporin water channels facilitate the bi-directional flow of water and small, neutral solutes down an osmotic gradient in all kingdoms of life. Over the last two decades, the availability of high-quality protein has underpinned progress in the structural and functional characterization of these water channels. In particular, recombinant protein technology has guaranteed the supply of aquaporin samples that were of sufficient quality and quantity for further study. Here we review the features of successful expression, purification and characterization strategies that have underpinned these successes and that will drive further breakthroughs in the field. Overall, Escherichia coli is a suitable host for prokaryotic isoforms, while Pichia pastoris is the most commonly-used recombinant host for eukaryotic variants. Generally, a two-step purification procedure is suitable after solubilization in glucopyranosides and most structures are determined by X-ray following crystallization.
Topics: Aquaporins; Crystallography, X-Ray; Escherichia coli; Models, Molecular; Saccharomycetales
PubMed: 34019902
DOI: 10.1016/j.bbamem.2021.183650 -
Kidney International Jun 1996Aquaporins (AQPs) are a newly recognized family of transmembrane proteins that function as molecular water channels. At least four aquaporins are expressed in the kidney... (Review)
Review
Aquaporins (AQPs) are a newly recognized family of transmembrane proteins that function as molecular water channels. At least four aquaporins are expressed in the kidney where they mediate rapid water transport across water-permeable epithelia and play critical roles in urinary concentrating and diluting processes. AQP1 is constitutively expressed at extremely high levels in the proximal tubule and descending limb of Henle's loop. AQP2, -3 and -4 are expressed predominantly in the collecting duct system. AQP2 is the predominant water channel in the apical plasma membrane and AQP3 and -4 are found in the basolateral plasma membrane. Short-term regulation of collecting duct water permeability by vasopressin is largely a consequence of regulated trafficking of AQP2-containing vesicles to and from the apical plasma membrane.
Topics: Aquaporin 1; Aquaporin 2; Aquaporin 3; Aquaporin 4; Aquaporin 6; Aquaporins; Ion Channels; Kidney Tubules; Water
PubMed: 8743483
DOI: 10.1038/ki.1996.253 -
Cells Jan 2019Water homeostasis is fundamental for cell survival. Transport of water across cellular membranes is governed by aquaporins-tetrameric integral membrane channels that are... (Review)
Review
Water homeostasis is fundamental for cell survival. Transport of water across cellular membranes is governed by aquaporins-tetrameric integral membrane channels that are highly conserved throughout the prokaryotic and eukaryotic kingdoms. In eukaryotes, specific regulation of these channels is required and is most commonly carried out by shuttling the protein between cellular compartments (trafficking) or by opening and closing the channel (gating). Structural and functional studies have revealed phosphorylation as a ubiquitous mechanism in aquaporin regulation by both regulatory processes. In this review we summarize what is currently known about the phosphorylation-dependent regulation of mammalian aquaporins. Focusing on the water-specific aquaporins (AQP0⁻AQP5), we discuss how gating and trafficking are controlled by phosphorylation and how phosphorylation affects the binding of aquaporins to regulatory proteins, thereby highlighting structural details and dissecting the contribution of individual phosphorylated residues when possible. Our aim is to provide an overview of the mechanisms behind how aquaporin phosphorylation controls cellular water balance and to identify key areas where further studies are needed.
Topics: Amino Acid Sequence; Animals; Aquaporins; Humans; Mammals; Models, Biological; Phosphorylation; Protein Binding
PubMed: 30678081
DOI: 10.3390/cells8020082 -
International Journal of Molecular... Dec 2017Water is the major component of cells and tissues, and the movement of water across the cell membrane is a fundamental property of life. Until the discovery of the first... (Review)
Review
Water is the major component of cells and tissues, and the movement of water across the cell membrane is a fundamental property of life. Until the discovery of the first water channel, aquaporin, it was long assumed that the transport of water was due to simple diffusion through the lipid bilayer membrane that encloses cells. Aquaporin (AQP) molecules were first discovered in the human uterus in 1994, and since then several studies have investigated these channels in the female reproductive system. The expressions of AQPs have been proven in the reproductive system. Their levels are altered during the implantation process, both in the uterus and the fetal cells, and participate in the control of the flow of amniotic fluid. They seem to be very important for the normal placental functions. AQPs are present during parturition, participating in the control of pregnant myometrial contractions and cervical ripening. However, most of the physiological and regulatory roles of AQPs are not clarified in the reproductive tract. Furthermore, no satisfactory knowledge is available about their sensitivities to different drugs. AQP-selective ligands may contribute to the development of new drug candidates and the therapy of several reproductive disorders.
Topics: Amniotic Fluid; Animals; Aquaporins; Female; Gene Expression Regulation; Genitalia, Female; Humans; Ligands; Parturition; Pregnancy
PubMed: 29194396
DOI: 10.3390/ijms18122593 -
Biological Research Jan 2018Aquaporins (AQP) are channel proteins belonging to the Major Intrinsic Protein (MIP) superfamily that play an important role in plant water relations. The main role of... (Review)
Review
Aquaporins (AQP) are channel proteins belonging to the Major Intrinsic Protein (MIP) superfamily that play an important role in plant water relations. The main role of aquaporins in plants is transport of water and other small neutral molecules across cellular biological membranes. AQPs have remarkable features to provide an efficient and often, specific water flow and enable them to transport water into and out of the cells along the water potential gradient. Plant AQPs are classified into five main subfamilies including the plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), nodulin 26 like intrinsic proteins (NIPs), small basic intrinsic proteins (SIPs) and X intrinsic proteins (XIPs). AQPs are localized in the cell membranes and are found in all living cells. However, most of the AQPs that have been described in plants are localized to the tonoplast and plasma membranes. Regulation of AQP activity and gene expression, are also considered as a part of the adaptation mechanisms to stress conditions and rely on complex processes and signaling pathways as well as complex transcriptional, translational and posttranscriptional factors. Gating of AQPs through different mechanisms, such as phosphorylation, tetramerization, pH, cations, reactive oxygen species, phytohormones and other chemical agents, may play a key role in plant responses to environmental stresses by maintaining the uptake and movement of water in the plant body.
Topics: Aquaporins; Biological Transport; Gene Expression; Plants; Stress, Physiological
PubMed: 29338771
DOI: 10.1186/s40659-018-0152-0 -
Plant, Cell & Environment Oct 2020The phosphorylation state of two serine residues within the C-terminal domain of AtPIP2;1 (S280, S283) regulates its plasma membrane localization in response to salt and...
The phosphorylation state of two serine residues within the C-terminal domain of AtPIP2;1 (S280, S283) regulates its plasma membrane localization in response to salt and osmotic stress. Here, we investigated whether the phosphorylation state of S280 and S283 also influence AtPIP2;1 facilitated water and cation transport. A series of single and double S280 and S283 phosphomimic and phosphonull AtPIP2;1 mutants were tested in heterologous systems. In Xenopus laevis oocytes, phosphomimic mutants AtPIP2;1 S280D, S283D, and S280D/S283D had significantly greater ion conductance for Na and K , whereas the S280A single phosphonull mutant had greater water permeability. We observed a phosphorylation-dependent inverse relationship between AtPIP2;1 water and ion transport with a 10-fold change in both. The results revealed that phosphorylation of S280 and S283 influences the preferential facilitation of ion or water transport by AtPIP2;1. The results also hint that other regulatory sites play roles that are yet to be elucidated. Expression of the AtPIP2;1 phosphorylation mutants in Saccharomyces cerevisiae confirmed that phosphorylation influences plasma membrane localization, and revealed higher Na accumulation for S280A and S283D mutants. Collectively, the results show that phosphorylation in the C-terminal domain of AtPIP2;1 influences its subcellular localization and cation transport capacity.
Topics: Animals; Animals, Genetically Modified; Aquaporins; Arabidopsis; Arabidopsis Proteins; Ion Channels; Oocytes; Phosphorylation; Water; Xenopus laevis
PubMed: 32678928
DOI: 10.1111/pce.13851 -
Annals of Nutrition & Metabolism 2017The movement of water into and out of cells is a fundamental biological process that is essential for life. Such water movement not only regulates the activity of... (Review)
Review
The movement of water into and out of cells is a fundamental biological process that is essential for life. Such water movement not only regulates the activity of individual cells but also is responsible for the functioning of many organ systems and for maintaining whole body water balance. It had long been suspected that water movement across biological cell membranes was in some way enhanced or facilitated by pores or channels, but the search to identify these channels was long and tedious. As is often the case in science, the secret of the water channel was eventually discovered by chance in 1992 by Peter Agre and his colleagues at the Johns Hopkins University in Baltimore, who were working on red blood cell membrane proteins. This "first" water channel was originally named CHIP28 and is now known as aquaporin 1. Agre received the Nobel Prize in Chemistry in 2003 for this discovery. There are currently 13 known aquaporins in mammals, distributed in most tissues, but many more have been identified in lower organisms and in the plant kingdom. The involvement of aquaporins in processes such as urinary concentration and body fluid homeostasis, brain function, glandular secretion, skin hydration, male fertility, hearing, vision, and most important body functions that can be imagined are now all under intense scientific scrutiny. Moreover, defects in aquaporin function have been related to various disease conditions and pathological states. This brief review will discuss their background, discovery, and function in selected bodily processes, especially focusing on hydration.
Topics: Animals; Aquaporins; Drinking; Homeostasis; Humans; Kidney; Models, Animal; Organism Hydration Status
PubMed: 28614812
DOI: 10.1159/000463061 -
Biochimica Et Biophysica Acta May 2014The presence of water channel proteins, aquaporins (AQPs), in the brain led to intense research in understanding the underlying roles of each of them under normal... (Review)
Review
BACKGROUND
The presence of water channel proteins, aquaporins (AQPs), in the brain led to intense research in understanding the underlying roles of each of them under normal conditions and pathological conditions.
SCOPE OF REVIEW
In this review, we summarize some of the recent knowledge on the 3 main AQPs (AQP1, AQP4 and AQP9), with a special focus on AQP4, the most abundant AQP in the central nervous system.
MAJOR CONCLUSIONS
AQP4 was most studied in several brain pathological conditions ranging from acute brain injuries (stroke, traumatic brain injury) to the chronic brain disease with autoimmune neurodegenerative diseases. To date, no specific therapeutic agents have been developed to either inhibit or enhance water flux through these channels. However, experimental results strongly underline the importance of this topic for future investigation. Early inhibition of water channels may have positive effects in prevention of edema formation in brain injuries but at later time points during the course of a disease, AQP is critical for clearance of water from the brain into blood vessels.
GENERAL SIGNIFICANCE
Thus, AQPs, and in particular AQP4, have important roles both in the formation and resolution of edema after brain injury. The dual, complex function of these water channel proteins makes them an excellent therapeutic target. This article is part of a Special Issue entitled Aquaporins.
Topics: Aquaporins; Body Water; Brain Diseases; Humans
PubMed: 24513456
DOI: 10.1016/j.bbagen.2013.10.032 -
Pharmacological Research Sep 2022Aquaporin is a membrane channel protein widely expressed in body tissues, which can control the input and output of water in cells. AQPs are differentially expressed in... (Review)
Review
Aquaporin is a membrane channel protein widely expressed in body tissues, which can control the input and output of water in cells. AQPs are differentially expressed in different cardiovascular tissues and participate in water transmembrane transport, cell migration, metabolism, inflammatory response, etc. The aberrant expression of AQPs highly correlates with the onset of ischemic heart disease, myocardial ischemia-reperfusion injury, heart failure, etc. Despite much attention to the regulatory role of AQPs in the cardiovascular system, the translation of AQPs into clinical application still faces many challenges, including clarification of the localization of AQPs in the cardiovascular system and mechanisms mediating cardiovascular pathophysiology, as well as the development of cardiovascular-specific AQPs modulators.Therefore, in this study, we comprehensively reviewed the critical roles of AQP family proteins in maintaining cardiovascular homeostasis and described the underlying mechanisms by which AQPs mediated the outcomes of cardiovascular diseases. Meanwhile, AQPs serve as important therapeutic targets, which provide a wide range of opportunities to investigate the mechanisms of cardiovascular diseases and the treatment of those diseases.
Topics: Aquaporins; Biological Transport; Cardiovascular Diseases; Heart; Humans; Water
PubMed: 35905892
DOI: 10.1016/j.phrs.2022.106363