Aquaporins

The aquaporin field has matured at an exceptionally fast pace and we are at the verge to develop serious strategies to therapeutically modulate aquaporin function directly or via regulatory networks. Key prerequisites are available today: i. a considerable (and growing) number of aquaporin crystal structures for the rational design of inhibitory molecules, ii. elaborate molecular dynamics simulation techniques for theoretical analyses of selectivity mechanisms and docking experiments, iii. comprehensive data on aquaporin immunohistochemistry, iv. aquaporin knockout animals for physiological studies, and v. assay systems for compound library screenings. The structure of this volume on aquaporins follows the points laid out above and thus covers the developments from basic research to potential pharmacological use. Situated between pharmacology textbooks and recent scientific papers this book provides a timely overview for readers from the fundamental as well as the applied disciplines.

Since the discovery of Aquaporin-1 (AQP1) as a water channel, many studies have revealed the importance of aquaporins in mammalian physiology and pathophysiology as well as plant and microbial biology. The studies have also shown aquaporins as potential drug targets and targets for improving crop properties. Written by an international group of contributors at the forefront of the field, Aquaporins in Health and Disease: New Molecular Targets for Drug Discovery presents the latest research advances in aquaporins and other major intrinsic protein (MIP) channels. The first section of the book describes the general concepts of aquaporin channel function, genomic research, structure-function analysis of aquaporins and glycerol facilitators, and regulation by gating and trafficking, including yeast aquaporin regulation and function. The second section discusses the physiological and pathophysiological roles of aquaporins in humans and microbes. The final section covers the development of inhibitors of aquaporin function. The book’s epilogue offers future perspectives and directions, mainly in the area of aquaporin-based diagnostics and therapeutics. Stimulating future research on this important protein family, this book facilitates a paradigm shift in the understanding and roles of aquaporin membrane proteins in all biological settings. It encourages scientists to develop novel approaches for the treatment of human diseases based on aquaporin function or dysfunction.

This book provides a state-of-the-art report on our current understanding of aquaporins and the future direction of the field. Aquaporins (AQPs) are a group of water-channel proteins that are specifically permeable to water and other small molecules, such as glycerol and urea. To date thirteen water-channel proteins (AQP0 – AQP12) have been cloned and the mechanisms and physiological functions of water transport across biological membranes have long been the subject of interest. Recent advances in the molecular biology and physiology of water transport have yielded new insights into how and why water moves across cell membranes, and studies on aquaporin knockout mouse models suggest that aquaporins are involved in the development of some diseases and they may be useful targets of research into selective-inhibitor drugs. By focusing on the advances made over the last 30 years in the biophysics, genetics, protein structure, molecular biology, physiology, pathophysiology and pharmacology of aquaporins in mammalian cell membranes, this book provides novel insights into further mechanisms and the physiological significance of water and some small molecule transport in mammals in order to stimulate further research in new directions. In the second version, fourteen chapters will be updated base on the most recent research articles. Ten new chapters will be added.

Aquaporins are channel proteins that facilitate the diffusion of water and small uncharged solutes across cellular membranes. Plant aquaporins form a large family of highly divergent proteins that are involved in many different physiological processes. This book will summarize the recent advances regarding plant aquaporins, their phylogeny, structure, substrate specificity, mechanisms of regulation and roles in various important physiological processes related to the control of water flow and small solute distribution at the cell, tissue and plant level in an ever-changing environment.

Aquaporins (AQPs), a class of integral membrane proteins, form channels facilitating movement of water and many other solutes. In solute transport systems of all living organisms including plants, animals and fungi, AQPs play a vital role. Plants contain a much higher number of AQP genes compared to animals, the likely consequence of genome duplication events and higher ploidy levels. As a result of duplication and subsequent diversification, plant AQPs have evolved several subfamilies with very diverse functions. Plant AQPs are highly selective for specific solutes because of their unique structural features. For instance, ar/R selectivity filters and NPA domains have been found to be key elements in governing solute permeability through the AQP channels. Combination of conserved motifs and specific amino acids influencing pore morphology appears to regulate the permeability of specific solutes such as water, urea, CO2, H2O2, boric acid, silicic acid and many more. The discovery of novel AQPs has been accelerated over the last few years with the increasing availability of genomic and transcriptomic data. The expanding number of well characterised AQPs provides opportunities to understand factors influencing water transport, nutritional uptake, and elemental balance. Homology-based search tools and phylogenetic analyses offer efficient strategies for AQP identification. Subsequent characterization can be based on different approaches involving proteomics, genomics, and transcriptomic tools. The combination of these technological advances make it possible to efficiently study the inter-dependency of AQPs, regulation through phosphorylation and reversible phosphorylation, networking with other transporters, structural features, pH gating systems, trafficking and degradation. Several studies have supported the role of AQPs in differential phenotypic responses to abiotic and biotic stress in plants. Crop improvement programs aiming for the development of cultivars with higher tolerance against stresses like drought, flooding, salinity and many biotic diseases, can explore and exploit the finely tuned AQP-regulated transport system. For instance, a promising approach in crop breeding programs is the utilization of genetic variation in AQPs for the development of stress tolerant cultivars. Similarly, transgenic and mutagenesis approaches provide an opportunity to better understand the AQP transport system with subsequent applications for the development of climate-smart drought-tolerant cultivars. The contributions to this Frontiers in Plant Science Research Topic have highlighted the evolution and phylogenetic distribution of AQPs in several plant species. Numerous aspects of regulation that seek to explain AQP-mediated transport system have been addressed. These contributions will help to improve our understanding of AQPs and their role in important physiological aspects and will bring AQP research closer to practical applications.

Since the discovery of Aquaporin-1 (AQP1) as a water channel, many studies have revealed the importance of aquaporins in mammalian physiology and pathophysiology as well as plant and microbial biology. The studies have also shown aquaporins as potential drug targets and targets for improving crop properties. Written by an international group of contributors at the forefront of the field, Aquaporins in Health and Disease: New Molecular Targets for Drug Discovery presents the latest research advances in aquaporins and other major intrinsic protein (MIP) channels. The first section of the book describes the general concepts of aquaporin channel function, genomic research, structure-function analysis of aquaporins and glycerol facilitators, and regulation by gating and trafficking, including yeast aquaporin regulation and function. The second section discusses the physiological and pathophysiological roles of aquaporins in humans and microbes. The final section covers the development of inhibitors of aquaporin function. The book’s epilogue offers future perspectives and directions, mainly in the area of aquaporin-based diagnostics and therapeutics. Stimulating future research on this important protein family, this book facilitates a paradigm shift in the understanding and roles of aquaporin membrane proteins in all biological settings. It encourages scientists to develop novel approaches for the treatment of human diseases based on aquaporin function or dysfunction.

By living in a 'world of water' fish are exposed to major challenges in maintaining water homeostasis. These are opposite in nature for fish living in marine and freshwater milieus; however, in both cases threatening, obligatory water fluxes due to global osmotic gradients must be compensated by opposite fluxes, driven by body fluid filtration and/or locally created osmotic gradients. In general, water may pass epithelia that are hydrophobic in nature by para- and/or transcellular pathways, the former mainly defined by the characteristics of tight junctions, the latter determined by the combined permeability of apical and baso-lateral cellular membranes. Transcellular water transport may occur by simple diffusion through lipid bilayers or become markedly improved by insertion of plasma membrane integral channel proteins of the Aquaporin (AQP) family. In mammals, 13 AQP subfamilies are present and several of these have been investigated structurally and functionally in >5000 publications since their discovery in 1992 by Agre and colleagues. The first paper on AQPs in fish appeared in 2000 (Cutler and Cramb) but surprisingly few papers have addressed AQPs in fishes and other non-mammalian vertebrate classes since then. In zebrafish, 18 genes encode AQPs with homology to all but a few of the mammalian isoforms. Only few of these isoforms have been studied to some extent in this and other species. AQPs most certainly play distinct osmoregulatory roles in fish as they do in mammals - both at the cellular and organismal level. However, there is a considerable lack of information from the fish world on this topic. At present, only ca. 50 papers have addressed AQPs in fish - most of these being concerned with basic investigations of isoform expression in various tissues of different teleosts. This Research Topic will bring together original information as well as bring the field up-to-date on topics related to 'Aquaporins in fish - expression, localization and functional dynamics', hopefully thereby stimulating new research in this area. Contributions within the following areas are welcomed: • Molecular biology of water transport • AQP physiology and functionality (in vitro and in vivo studies) • Cellular and subcellular localization of AQPs • AQPs and cellular volume regulation/osmosensing • AQPs and transepithelial water transport in kidney tubules and intestinal segments • Endocrine regulation of AQPs • Cellular trafficking of AQPs • Pharmacological inhibition of AQPs • The role of AQPs in handling "non-water" substances (toxic, waste etc.) • Mini-reviews identifying areas of special interest.