BBA - General Subjects (v.1840, #5)
Editorial Board (i).
Preface to the 2014 Aquaporins Special Issue by Susanna Törnroth-Horsefield (1465).
Foreword to 2014 Aquaporins Special Issue by Peter Agre; Susanna Törnroth-Horsefield (1466-1467).
Diversity and evolution of membrane intrinsic proteins by Federico Abascal; Iker Irisarri; Rafael Zardoya (1468-1481).
Membrane intrinsic proteins (MIPs) are the proteins in charge of regulating water transport into cells. Because of this essential function, the MIP family is ancient, widespread, and highly diverse.The rapidly accumulating genomic and transcriptomic data from previously poorly known groups such as unicellular eukaryotes, fungi, green algae, mosses, and non-vertebrate animals are contributing to expand our view of MIP evolution throughout the diversity of life. Here, by analyzing more than 1700 sequences, we provide an updated and comprehensive phylogeny of MIPsThe reconstructed phylogeny supports (i) deep orthology of X intrinsic proteins (XIPs; present from unicellular eukaryotes to plants); (ii) that the origin of small intrinsic proteins (SIPs) traces back to the common ancestor of all plants; and (iii) the expansion of aquaglyceroporins (GLPs) in Oomycetes, as well as their loss in vascular plants and in the ancestor of endopterygote insects. Additionally, conserved positions in the protein, and residues involved in glycerol selectivity are reviewed within a phylogenetic framework. Furthermore, functional diversification of human and Arabidopsis paralogs are analyzed in an evolutionary genomic context.Our results show that while bacteria and archaea generally function with one copy of each a water channel (aquaporin or AQP) and a GLP, recurrent independent expansions have greatly diversified the structures and functions of the different members of both MIP paralog subfamilies throughout eukaryote evolution (and not only in flowering plants and vertebrates, as previously thought). This article is part of a Special Issue entitled Aquaporins.Display Omitted
Keywords: Membrane intrinsic protein; Aquaporin; Evolutionary relationship; Molecular phylogeny;
Yeast reveals unexpected roles and regulatory features of aquaporins and aquaglyceroporins by Doryaneh Ahmadpour; Cecilia Geijer; Markus J. Tamás; Karin Lindkvist-Petersson; Stefan Hohmann (1482-1491).
The yeast Saccharomyces cerevisiae provides unique opportunities to study roles and regulation of aqua/glyceroporins using frontline tools of genetics and genomics as well as molecular cell and systems biology. S. cerevisiae has two similar orthodox aquaporins. Based on phenotypes mediated by gene deletion or overexpression as well as on their expression pattern, the yeast aquaporins play important roles in key aspects of yeast biology: establishment of freeze tolerance, during spore formation as well as determination of cell surface properties for substrate adhesion and colony formation. Exactly how the aquaporins perform those roles and the mechanisms that regulate their function under such conditions remain to be elucidated. S. cerevisiae also has two different aquaglyceroporins. While the role of one of them, Yfl054c, remains to be determined, Fps1 plays critical roles in osmoregulation by controlling the accumulation of the osmolyte glycerol. Fps1 communicates with two osmo-sensing MAPK signalling pathways to perform its functions but the details of Fps1 regulation remain to be determined.Several phenotypes associated with aqua/glyceroporin function in yeasts have been established. However, how water and glycerol transport contribute to the observed effects is not understood in detail. Also many of the basic principles of regulation of yeast aqua/glyceroporins remain to be elucidated.Studying the yeast aquaporins and aquaglyceroporins offers rich insight into the life style, evolution and adaptive responses of yeast and rewards us with discoveries of unexpected roles and regulatory mechanisms of members of this ancient protein family. This article is part of a Special Issue entitled Aquaporins.
Keywords: Aquaporin; Osmoregulation; Freeze tolerance; Stress resistance; Signal transduction; MAPK pathway;
Human aquaporins: Regulators of transcellular water flow by Rebecca E. Day; Philip Kitchen; David S. Owen; Charlotte Bland; Lindsay Marshall; Alex C. Conner; Roslyn M. Bill; Matthew T. Conner (1492-1506).
Emerging evidence supports the view that (AQP) aquaporin water channels are regulators of transcellular water flow. Consistent with their expression in most tissues, AQPs are associated with diverse physiological and pathophysiological processes.AQP knockout studies suggest that the regulatory role of AQPs, rather than their action as passive channels, is their critical function. Transport through all AQPs occurs by a common passive mechanism, but their regulation and cellular distribution varies significantly depending on cell and tissue type; the role of AQPs in cell volume regulation (CVR) is particularly notable. This review examines the regulatory role of AQPs in transcellular water flow, especially in CVR. We focus on key systems of the human body, encompassing processes as diverse as urine concentration in the kidney to clearance of brain oedema.AQPs are crucial for the regulation of water homeostasis, providing selective pores for the rapid movement of water across diverse cell membranes and playing regulatory roles in CVR. Gating mechanisms have been proposed for human AQPs, but have only been reported for plant and microbial AQPs. Consequently, it is likely that the distribution and abundance of AQPs in a particular membrane is the determinant of membrane water permeability and a regulator of transcellular water flow.Elucidating the mechanisms that regulate transcellular water flow will improve our understanding of the human body in health and disease. The central role of specific AQPs in regulating water homeostasis will provide routes to a range of novel therapies. This article is part of a Special Issue entitled Aquaporins.Display Omitted
Keywords: Aquaporin regulation; Transcellular water flow; Homeostasis; Cell volume regulation; Regulatory volume increase; Regulatory volume decrease;
The role of mammalian superaquaporins inside the cell by Kenichi Ishibashi; Yasuko Tanaka; Yoshiyuki Morishita (1507-1512).
The mammalian two superaquaporins, AQP11 and AQP12, are present inside the cell and their null phenotypes in mice suggest their unusual functions.The surveyed literature on these superaquaporins and our unpublished data has been incorporated to speculate their roles.AQP11 and AQP12 have unique NPA boxes with a signature cysteine residue. Although some water permeability of AQP11 was demonstrated in liposomes and cultured cells, its permeability to glycerol is unknown. The function of AQP12 still remains to be clarified. AQP11 null mice develop polycystic kidneys following large intracellular vacuoles in the proximal tubule, which may be caused by ER stress or vesicle fusion failure. The role of AQP11 in the kidney and liver seems to alleviate the tissue damage and facilitate the recovery. Its expression in the sperm, thymus and brain suggests its potential roles in these organs in spite of the apparently normal null phenotype. Although AQP12 null mice appear normal, they suffer from severe pancreatitis, suggesting its role in the fusion of zymogen granules.As many issues are unsolved, the clarification of the function and roles of the superaquaporin may lead to the identification of new roles of AQPs. This article is part of a Special Issue entitled Aquaporins.
Keywords: Superaquaporin; Vesicle fusion; Tissue recovery; Polycystic kidney; Pancreatitis;
Aquaporins in the eye: Expression, function, and roles in ocular disease by Kevin L. Schey; Zhen Wang; Jamie L. Wenke; Ying Qi (1513-1523).
All thirteen known mammalian aquaporins have been detected in the eye. Moreover, aquaporins have been identified as playing essential roles in ocular functions ranging from maintenance of lens and corneal transparency to production of aqueous humor to maintenance of cellular homeostasis and regulation of signal transduction in the retina.This review summarizes the expression and known functions of ocular aquaporins and discusses their known and potential roles in ocular diseases.Aquaporins play essential roles in all ocular tissues. Remarkably, not all aquaporin function as a water permeable channel and the functions of many aquaporins in ocular tissues remain unknown. Given their vital roles in maintaining ocular function and their roles in disease, aquaporins represent potential targets for future therapeutic development.Since aquaporins play key roles in ocular physiology, an understanding of these functions is important to improving ocular health and treating diseases of the eye. It is likely that future therapies for ocular diseases will rely on modulation of aquaporin expression and/or function. This article is part of a Special Issue entitled Aquaporins.
Keywords: Aquaporin; Cornea; Lens; Retina; Glaucoma; Cataract;
Aquaporins in salivary glands and pancreas by Christine Delporte (1524-1532).
Salivary glands and pancreas are involved in saliva secretion, pancreatic fluid secretion and insulin secretion. These functions are essential for proper oral, pancreatic and glucose homeostasis. Aquaporins are water-permeable transmembrane protein involved in the physiology of these secretory gland functions.This review gives an overview of the morphology of salivary glands and pancreas, the expression and localization of aquaporins, the secretion roles and mechanisms, the physiological roles of aquaporins, and the role of aquaporins in pathophysiological conditions.Several aquaporins are expressed in salivary glands and pancreas, and some play important physiological roles. Modulation of aquaporin expression and/or trafficking may contribute to the pathogenesis of diseases affecting salivary glands and pancreas glands such as xerostomic conditions, pancreatic insufficiencies and diabetes.Aquaporins are involved in physiological and pathophysiological processes in salivary glands and pancreas. They could represent therapeutic targets for the treatment of diseases affecting the salivary glands and pancreas. This article is part of a Special Issue entitled Aquaporins.
Keywords: Aquaporin; Salivary gland; Pancreas; Physiology; Pathophysiology;
Renal aquaporins and water balance disorders by Marleen L.A. Kortenoeven; Robert A. Fenton (1533-1549).
Aquaporins (AQPs) are a family of proteins that can act as water channels. Regulation of AQPs is critical to osmoregulation and the maintenance of body water homeostasis. Eight AQPs are expressed in the kidney of which five have been shown to play a role in body water balance; AQP1, AQP2, AQP3, AQP4 and AQP7. AQP2 in particular is regulated by vasopressin.This review summarizes our current knowledge of the underlying mechanisms of various water balance disorders and their treatment strategies.Dysfunctions of AQPs are involved in disorders associated with disturbed water homeostasis. Hyponatremia with increased AQP levels can be caused by diseases with low effective circulating blood volume, such as congestive heart failure, or osmoregulation disorders such as the syndrome of inappropriate secretion of antidiuretic hormone. Treatment consists of fluid restriction, demeclocycline and vasopressin type-2 receptor antagonists. Decreased AQP levels can lead to diabetes insipidus (DI), characterized by polyuria and polydipsia. In central DI, vasopressin production is impaired, while in gestational DI, levels of the vasopressin-degrading enzyme vasopressinase are abnormally increased. Treatment consists of the vasopressin analogue dDAVP. Nephrogenic DI is caused by the inability of the kidney to respond to vasopressin and can be congenital, but is most commonly acquired, usually due to lithium therapy. Treatment consists of sufficient fluid supply, low-solute diet and diuretics.In recent years, our understanding of the underlying mechanisms of water balance disorders has increased enormously, which has opened up several possible new treatment strategies. This article is part of a Special Issue entitled Aquaporins.
Keywords: Aquaporin; Kidney; Diabetes insipidus; SIADH; Heart failure; Water transport;
Aquaporins in cancer by Domenico Ribatti; Girolamo Ranieri; Tiziana Annese; Beatrice Nico (1550-1553).
The aquaporins (AQPs) are a family of 13 small hydrophobic integral transmembrane water channel proteins involved in transcellular and transepithelial water movement, transport of fluid and cell migration.This review article summarizes our knowledge concerning the involvement of AQPs in tumor growth, angiogenesis and metastatic process.Tumor cells types express AQPs and a positive correlation exists between histological tumor grade and the AQP expression. Moreover, AQPs are involved also in tumor edema formation and angiogenesis in several solid and hematological tumors.AQPs inhibition in endothelial and tumor cells might limit tumor growth and spread, suggesting a potential therapeutic use in the treatment of tumors. This article is part of a Special Issue entitled Aquaporins.
Keywords: Angiogenesis; Aquaporins; Edema; Glioblastoma; Tumor growth;
Aquaporin and brain diseases by Jérôme Badaut; Andrew M. Fukuda; Amandine Jullienne; Klaus G. Petry (1554-1565).
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.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.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.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.
Keywords: Edema; Water channel; Neuroimaging; Neuroinflammation; Neurovascular unit; Blood–brain barrier;
Parasite aquaporins: Current developments in drug facilitation and resistance by Jie Song; Ellen Mak; Binghua Wu; Eric Beitz (1566-1573).
Although being situated in a niche, research on parasite aquaporins is a lively field that has provided new insight into basic aquaporin structure–function relationships and physiological roles of water and solute transport. Moreover, it bears the potential to find novel approaches to antiparasitic chemotherapy.Here, we summarize the current knowledge about the structure and substrate selectivity of aquaporins from protozoan and helminth parasites, review the current views on their physiological roles, and discuss their potency for chemotherapy.Parasite aquaporins fulfill highly diverse tasks in the physiology of the various organisms, yet their general protein structure is well conserved. Aquaporins are directly (antimonials) and indirectly (melarsoprol, pentamidine) linked to the uptake of antiparasitic drugs. Unfortunately, drug-like aquaporin inhibitors are still missing.Aquaporins expression levels determine the degree of parasite resistance against certain drugs. Further studies on parasite aquaporins may provide data about overcoming drug resistance mechanisms or even spark novel treatments. This article is part of a Special Issue entitled Aquaporins.
Keywords: Aquaporin; Water; Glycerol; Antimonials; Pentamidine; Parasite;
Plant aquaporins: Roles in plant physiology by Guowei Li; Véronique Santoni; Christophe Maurel (1574-1582).
Aquaporins are membrane channels that facilitate the transport of water and small neutral molecules across biological membranes of most living organisms.Here, we present comprehensive insights made on plant aquaporins in recent years, pointing to their molecular and physiological specificities with respect to animal or microbial counterparts.In plants, aquaporins occur as multiple isoforms reflecting a high diversity of cellular localizations and various physiological substrates in addition to water. Of particular relevance for plants is the transport by aquaporins of dissolved gases such as carbon dioxide or metalloids such as boric or silicic acid. The mechanisms that determine the gating and subcellular localization of plant aquaporins are extensively studied. They allow aquaporin regulation in response to multiple environmental and hormonal stimuli. Thus, aquaporins play key roles in hydraulic regulation and nutrient transport in roots and leaves. They contribute to several plant growth and developmental processes such as seed germination or emergence of lateral roots.Plants with genetically altered aquaporin functions are now tested for their ability to improve plant resistance to stresses. This article is part of a Special Issue entitled Aquaporins.
Keywords: Aquaporin; Genetic diversity; Hydraulics; Nutrient acquisition; Plant signaling; Root; Stress; Water transport;
Aquaglyceroporins: Generalized metalloid channels by Rita Mukhopadhyay; Hiranmoy Bhattacharjee; Barry P. Rosen (1583-1591).
Aquaporins (AQPs), members of a superfamily of transmembrane channel proteins, are ubiquitous in all domains of life. They fall into a number of branches that can be functionally categorized into two major sub-groups: i) orthodox aquaporins, which are water-specific channels, and ii) aquaglyceroporins, which allow the transport of water, non-polar solutes, such as urea or glycerol, the reactive oxygen species hydrogen peroxide, and gases such as ammonia, carbon dioxide and nitric oxide and, as described in this review, metalloids.This review summarizes the key findings that AQP channels conduct bidirectional movement of metalloids into and out of cells.As(OH)3 and Sb(OH)3 behave as inorganic molecular mimics of glycerol, a property that allows their passage through AQP channels. Plant AQPs also allow the passage of boron and silicon as their hydroxyacids, boric acid (B(OH)3) and orthosilicic acid (Si(OH)4), respectively. Genetic analysis suggests that germanic acid (GeO2) is also a substrate. While As(III), Sb(III) and Ge(IV) are toxic metalloids, borate (B(III)) and silicate (Si(IV)) are essential elements in higher plants.The uptake of environmental metalloids by aquaporins provides an understanding of (i) how toxic elements such as arsenic enter the food chain; (ii) the delivery of arsenic and antimony containing drugs in the treatment of certain forms of leukemia and chemotherapy of diseases caused by pathogenic protozoa; and (iii) the possibility that food plants such as rice could be made safer by genetically modifying them to exclude arsenic while still accumulating boron and silicon. This article is part of a Special Issue entitled Aquaporins.
Keywords: Metalloid; Antimonite; Arsenite; Boron; Silicon; Aquaglyceroporins;
Aquaporins and membrane diffusion of CO2 in living organisms by Ralf Kaldenhoff; Lei Kai; Norbert Uehlein (1592-1595).
Determination of CO2 diffusion rates in living cells revealed inconsistencies with existing models about the mechanisms of membrane gas transport. Mainly, these discrepancies exist in the determined CO2 diffusion rates of bio-membranes, which were orders of magnitudes below those for pure lipid bilayers or theoretical considerations as well as in the observation that membrane insertion of specific aquaporins was rescuing high CO2 transport rates. This effect was confirmed by functional aquaporin protein analysis in heterologous expression systems as well as in bacteria, plants and partly in mammals.This review summarizes the arguments in favor of and against aquaporin facilitated membrane diffusion of CO2 and reports about its importance for the physiology of living organisms.Most likely, the aquaporin tetramer forming an additional fifth pore is required for CO2 diffusion facilitation. Aquaporin tetramer formation, membrane integration and disintegration could provide a mechanism for regulation of cellular CO2 exchange. The physiological importance of aquaporin mediated CO2 membrane diffusion could be shown for plants and cyanobacteria and partly for mammals.Taking the mentioned results into account, consequences for our current picture of cell membrane transport emerge. It appears that in some or many instances, membranes might not be as permeable as it was suggested by current bio-membrane models, opening an additional way of controlling the cellular influx or efflux of volatile substances like CO2. This article is part of a Special Issue entitled Aquaporins.
Keywords: Aquaporin; Membrane permeability for CO2; Gas exchange; Aquaporin structure-function; CO2 conductance of aquaporins;
Aquaporin-facilitated transmembrane diffusion of hydrogen peroxide by Gerd P. Bienert; François Chaumont (1596-1604).
Hydrogen peroxide (H2O2) is an important signaling compound that has recently been identified as a new substrate for several members of the aquaporin superfamily in various organisms. Evidence is emerging about the physiological significance of aquaporin-facilitated H2O2 diffusion.This review summarizes current knowledge about aquaporin-facilitated H2O2 diffusion across cellular membranes. It focuses on physicochemical and experimental evidence demonstrating the involvement of aquaporins in the transport of this redox signaling compound and discusses the regulation and structural prerequisites of these channels to transmit this signal. It also provides perspectives about the potential importance of aquaporin-facilitated H2O2 diffusion processes and places this knowledge in the context of the current understanding of transmembrane redox signaling processes.Specific aquaporin isoforms facilitate the passive diffusion of H2O2 across biological membranes and control H2O2 membrane permeability and signaling in living organisms.Redox signaling is a very important process regulating the physiology of cells and organisms in a similar way to the well-characterized hormonal and calcium signaling pathways. Efficient transmembrane diffusion of H2O2, a key molecule in the redox signaling network, requires aquaporins and makes these channels important players in this signaling process. Channel-mediated membrane transport allows the fine adjustment of H2O2 levels in the cytoplasm, intracellular organelles, the apoplast, and the extracellular space, which are essential for it to function as a signal molecule. This article is part of a Special Issue entitled Aquaporins.
Keywords: Aquaporin; Transmembrane transport; Hydrogen peroxide; Signaling; Oxidative stress; Reactive oxygen species;
Water channel structures analysed by electron crystallography by Kazutoshi Tani; Yoshinori Fujiyoshi (1605-1613).
The mechanisms underlying water transport through aquaporin (AQP) have been debated for two decades. The water permeation phenomenon of AQP seems inexplicable because the Grotthuss mechanism does not allow for simultaneous fast water permeability and inhibition of proton transfer through the hydrogen bonds of water molecules.The AQP1 structure determined by electron crystallography provided the first insights into the proton exclusion mechanism despite fast water permeation. Although several studies have provided clues about the mechanism based on the AQP structure, each proposed mechanism remains incomplete. The present review is focused on AQP function and structure solved by electron crystallography in an attempt to fill the gaps between the findings in the absence and presence of lipids.Many AQP structures can be superimposed regardless of the determination method. The AQP fold is preserved even under conditions lacking lipids, but the water arrangement in the channel pore differs. The differences might be explained by dipole moments formed by the two short helices in the lipid bilayer. In addition, structure analyses of double-layered two-dimensional crystals of AQP suggest an array formation and cell adhesive function.Electron crystallography findings not only have contributed to resolve some of the water permeation mechanisms, but have also elucidated the multiple functions of AQPs in the membrane. The roles of AQPs in the brain remain obscure, but their multiple activities might be important in the regulation of brain and other biological functions. This article is part of a Special Issue entitled Aquaporins.Display Omitted
Keywords: Water channel; Aquaporin; Electron crystallography; Cryo-electron microscopy; Cell adhesion;
Unraveling aquaporin interaction partners by Jennie Sjöhamn; Kristina Hedfalk (1614-1623).
Insight into protein–protein interactions (PPIs) is highly desirable in order to understand the physiology of cellular events. This understanding is one of the challenges in biochemistry and molecular biology today, especially for eukaryotic membrane proteins where hurdles of production, purification and structural determination must be passed.We have explored the common strategies used to find medically relevant interaction partners of aquaporins (AQPs). The most frequently used methods to detect direct contact, yeast two-hybrid interaction assay and co-precipitation, are described together with interactions specifically found for the selected targets AQP0, AQP2, AQP4 and AQP5.The vast majority of interactions involve the aquaporin C-terminus and the characteristics of the interaction partners are strikingly diverse. While the well-established methods for PPIs are robust, a novel approach like bimolecular fluorescence complementation (BiFC) is attractive for screening many conditions as well as transient interactions. The ultimate goal is structural evaluation of protein complexes in order to get mechanistic insight into how proteins communicate at a molecular level.What we learn from the human aquaporin field in terms of method development and communication between proteins can be of major use for any integral membrane protein of eukaryotic origin. This article is part of a Special Issue entitled Aquaporins.
Keywords: Membrane protein; Aquaporin; Protein–protein interaction; Co-precipitation; Yeast two-hybrid interaction assay;