Aquaporins

Description

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. Preface Contents 1: Classification and Gene Structure of Aquaporins 1.1 Classification of Aquaporins 1.2 Isoforms of AQPs 1.2.1 Classical Aquaporins 1.2.1.1 AQP0 1.2.1.2 AQP1 1.2.1.3 AQP2 1.2.1.4 AQP4 1.2.1.5 AQP5 1.2.1.6 AQP6 1.2.2 Superaquaporins 1.2.2.1 AQP11 1.2.2.2 AQP12 1.2.3 AQP8-Type Aquaammoniaporins 1.2.3.1 AQP8 1.2.4 Aquaglyceroporins 1.2.4.1 AQP3 1.2.4.2 AQP7 1.2.4.3 AQP9 1.2.4.4 AQP10 1.3 Gene Structures of AQPs References 2: Protein Structure and Modification of Aquaporins 2.1 Introduction 2.2 Protein Structure of AQPs 2.2.1 Protein Structure the Classical AQPs 2.2.1.1 AQP0 2.2.1.2 AQP1 2.2.1.3 AQP2 2.2.1.4 AQP4 2.2.1.5 AQP5 2.2.2 Protein Structure of Aquaglyceroporins 2.2.2.1 AQP7 2.2.2.2 AQP10 2.2.3 Structure of Other AQPs 2.2.3.1 Plant AQPs 2.2.3.2 Eukaryotic Microorganism AQPs 2.2.3.3 Unicellular Protozoan AQPs 2.2.3.4 Prokaryotic AQPs 2.3 Protein Modification of AQPs 2.3.1 Protein Modification of AQP2 2.3.1.1 Phosphorylation 2.3.1.2 Ubiquitination 2.3.1.3 SUMOylation 2.3.1.4 Glutathionylation 2.3.1.5 Glycosylation 2.3.1.6 Other PTMs 2.3.2 PTM of Other AQPs 2.3.2.1 AQP0 2.3.2.2 AQP1 2.3.2.3 AQP4 2.3.2.4 AQP5 2.3.2.5 AQP8 2.4 Summary and Prospect References 3: Expression Regulation and Trafficking of Aquaporins 3.1 Introduction 3.2 Gating of AQPs 3.3 Trafficking of AQP2 to the Membrane 3.3.1 The cAMP-Mediated Effect of Vasopressin on AQP2 Trafficking 3.3.2 The Role of Calcium in Vasopressin-Induced AQP2 Trafficking 3.3.3 Vesicles Bearing AQP2 Transport to the Membrane 3.3.4 Docking and Fusion of Vesicles Bearing AQP2 with the Apical Membrane 3.3.5 Removal of AQP2 from the Membrane and Degradation 3.4 Transcriptional Regulation of AQP2 3.4.1 Transcription Factors Responsible for the Expression Regulation of Aqp2 3.4.2 AQP2-Targeting miRNAs in the Kidney 3.5 Epigenetic Regulation of AQP2 References 4: Transport Characteristics of Aquaporins 4.1 Water Transport Mediated by Aquaporins 4.2 Glycerol Transport Mediated by AQPs 4.3 Urea Transport Mediated by AQPs 4.4 Gas Transport Mediated by AQPs 4.4.1 Carbon Dioxide 4.4.2 Nitric Oxide 4.4.3 Ammonia 4.4.4 Oxygen (O2) 4.5 Other Molecules Transported by Aquaporins 4.5.1 Hydrogen Peroxide 4.5.2 Some Ions 4.5.3 Silicon 4.5.4 Antimonite and Arsenite References 5: Non-Transport Functions of Aquaporins 5.1 AQPs in Cell Migration 5.2 AQPs in Central Neural System (CNS) 5.2.1 AQP4 in Brain Edema 5.2.2 AQP4 in Neuroexcitation 5.3 AQPs in Fat Metabolism 5.4 AQP and Cell Proliferation 5.5 AQPs in Inflammation 5.5.1 AQPs and Lung Inflammation 5.5.2 AQPs and Digestive System Inflammation 5.5.3 AQPs and Neuroinflammation 5.5.4 AQPs and Arthritis 5.5.5 AQPs and Liver Inflammation 5.6 Conclusion References 6: Evolutionary Overview of Aquaporin Superfamily 6.1 Introduction 6.2 Classification of AQP Superfamily 6.2.1 Dichotomy Between Plasma Membrane AQP and Intracellular AQP 6.2.2 Classification Based on the NPA Box Domain 6.2.3 Correlation to the Selective Filter (SF) of AQP Channel 6.3 Putative Evolution of AQP Superfamily 6.3.1 Overview of Gene Evolution 6.3.2 The Relationship Between AQP1-Like and AQP3-Like 6.3.3 Evolution of AQP3-Like 6.3.4 The Origin of AQP8-Like and AQP11-Like 6.4 Perspectives References 7: Aquaporins in Nervous System 7.1 Introduction 7.2 Expression of AQPs in Nervous System 7.2.1 AQPs in the Central Nervous System 7.2.1.1 AQP1 7.2.1.2 AQP3 7.2.1.3 AQP4 7.2.1.4 AQP5 7.2.1.5 AQP6 7.2.1.6 AQP7 7.2.1.7 AQP8 7.2.1.8 AQP9 7.2.1.9 AQP11 7.2.2 AQPs in the Peripheral Nervous System 7.2.2.1 AQP1 7.2.2.2 AQP2 7.2.2.3 AQP4 7.3 Functions of AQPs in Nervous System 7.3.1 CNS Water Balance 7.3.2 Clearance of ISF Substances 7.3.3 Spatial Buffering of Extracellular Potassium 7.3.4 Calcium Signal Transduction 7.3.5 Regulation of Neurotransmission 7.3.6 Synaptic Plasticity 7.3.7 Adult Neurogenesis 7.3.8 Energy Metabolism 7.3.9 Other Functions 7.4 AQPs in Diseases in Nervous System 7.4.1 Cerebral Edema 7.4.2 Neuromyelitis Optica 7.4.3 Brain Tumor 7.4.4 Alzheimer´s Disease 7.4.5 Other Diseases in Nervous System 7.5 Modulators of AQPs in the CNS 7.6 Future Directions References 8: Aquaporins in Cardiovascular System 8.1 Introduction 8.2 Expression and Physiological Function of AQPs in the Cardiovascular System 8.2.1 AQP1 8.2.2 AQP4 8.2.3 AQP7 8.2.4 AQP9 8.3 AQPs and Cardiovascular Disease 8.3.1 Cerebral Ischemia 8.3.2 Congestive Heart Failure (CHF) 8.3.3 Hypertension 8.3.4 Pulmonary Hypertension 8.3.5 Angiogenesis 8.4 Summary References 9: Aquaporins in Respiratory System 9.1 Introduction 9.2 Expression of AQPs in Lungs and Airways 9.3 Functions of AQPs in Lung Fluid Transport 9.3.1 Alveolar Fluid Balance 9.3.2 Airway Fluid Balance 9.3.3 Pleural Fluid Balance 9.3.4 Submucosal Gland Secretion 9.4 AQPs in Respiratory Diseases 9.4.1 Lung Cancer Development 9.4.2 Lung Inflammation/Lung Injury 9.4.3 Asthma 9.5 Summary References 10: Aquaporins in Digestive System 10.1 Introduction 10.2 Expression of AQPs in the Gastrointestinal Tract and Digestive Glands 10.2.1 Aquaporin Subfamily 10.2.1.1 AQP1 10.2.1.2 AQP4 10.2.1.3 AQP5 10.2.1.4 AQP8 10.2.2 Aquaglyceroporin Subfamily 10.2.2.1 AQP3 10.2.2.2 AQP7 10.2.2.3 AQP9 10.2.2.4 AQP10 10.2.3 Superaquaporin Subfamily 10.2.3.1 AQP12 10.3 Functions of AQPs in the Digestive System 10.3.1 Fat Digestion 10.3.2 Digestive Fluid Secretion 10.3.3 Water Absorption 10.3.4 Intestinal Barrier 10.3.5 Insulin Secretion 10.3.6 Glycerol Metabolism 10.4 AQPs and Digestive Diseases 10.4.1 Cancer 10.4.2 Sjogren´s Syndrome 10.4.3 Pancreatitis 10.4.4 Liver Disease 10.4.5 Inflammatory Bowel Disease (IBD) 10.5 Conclusion References 11: Aquaporins in Urinary System 11.1 Introduction 11.2 Expression and Localization of AQPs in Urinary System 11.2.1 AQP1 11.2.2 AQP2 11.2.3 AQP3 11.2.4 AQP4 11.2.5 AQP5 11.2.6 AQP6 11.2.7 AQP7 11.2.8 AQP8 11.2.9 AQP9 11.2.10 AQP11 11.3 Functions of AQPs in Urinary System 11.3.1 AQP1 11.3.2 AQP2 11.3.3 AQP3 11.3.4 AQP4 11.3.5 AQP5 11.3.6 AQP6 11.3.7 AQP7 11.3.8 AQP8 11.3.9 AQP11 11.4 AQPs in Renal Diseases 11.4.1 Nephrogenic Diabetes Insipidus 11.4.2 Polycystic Kidney Disease 11.4.3 Acute Kidney Injury 11.4.4 Epithelial-Mesenchymal Transition and Fibrosis 11.4.5 Tumors 11.4.6 Pyelonephritis and IgA Nephropathy 11.4.7 Chronic Kidney Diseases References 12: Aquaporins in Reproductive System 12.1 Aquaporins in the Male Reproductive System 12.1.1 Water Transport in the Male Reproductive System 12.1.2 Aquaporins in Testis 12.1.3 Aquaporins in Sperm 12.1.4 Aquaporins in Efferent Ducts 12.1.5 Aquaporins in Epididymis 12.1.6 Aquaporins in Vas Deferens 12.1.7 Aquaporins in Male Accessory Glands 12.2 Aquaporins in the Female Reproductive System 12.2.1 Aquaporins in Vagina 12.2.2 Aquaporins in Cervix 12.2.3 Aquaporins in Uterus 12.2.4 Aquaporins in Oviduct 12.2.5 Aquaporins in Ovary 12.2.6 Aquaporins in Oocyte 12.3 Aquaporins and Sperm Cryopreservation 12.4 Aquaporins and Reproductive Diseases 12.4.1 Varicocele 12.4.2 Endometriosis 12.4.3 Cervical Cancer 12.5 Conclusions and Prospects References 13: Aquaporins in Immune System 13.1 Introduction 13.2 Expression of AQPs in Immune System 13.3 Functions of AQPs in Immune System 13.3.1 Immune Cell Priming 13.3.2 Migration, Phagocytosis, and Antigen Uptake of Immune Cells 13.3.3 Inflammatory Activation 13.3.4 Other Aspects 13.4 AQPs and Immune Disease 13.5 Conclusion and Prospect References 14: Aquaporins in Eye 14.1 Introduction 14.2 Expression of AQPs in Eye 14.2.1 Cornea 14.2.2 Trabecular Meshwork 14.2.3 Ciliary Body 14.2.4 Lens 14.2.5 Retina 14.2.6 Lacrimal Gland 14.3 Functional Abnormality of AQPs in Eye and Diseases References 15: Aquaporins in Skin 15.1 Introduction 15.2 Expression of AQPs in Different Layers of Skin 15.2.1 AQPs in Epidermis 15.2.2 AQPs in Dermis and Hypodermis 15.3 Functions of AQPs in Different Layers of Skin 15.3.1 Functions of AQPs in Epidermis 15.3.2 Functions of AQPs in Dermis and Hypodermis 15.4 AQPs in Skin Diseases 15.4.1 Xeroderma and Skin Dryness 15.4.2 Psoriasis 15.4.3 Vitiligo 15.4.4 Dermatitis 15.4.5 Skin Tumors 15.4.6 Palmoplantar Keratoderma 15.4.7 Systemic Sclerosis 15.4.8 Wound Healing 15.5 Summary References 16: Aquaporins in Glandular Secretion 16.1 Role of AQPs in Secretory Glands Located within the Gastrointestinal Tract 16.1.1 Salivary Glands 16.1.2 Gastric Glands 16.1.3 Duodenal Brunner´s Gland 16.1.4 Liver, Bile Ducts, and Gallbladder 16.1.4.1 Liver 16.1.4.2 Bile Ducts 16.1.4.3 Gallbladder 16.1.5 Intestinal Goblet Cells 16.1.6 Exocrine Pancreas 16.1.7 Endocrine Pancreas 16.2 Airway Submucosal Glands 16.3 Lacrimal Glands 16.4 Mammary Glands 16.5 Eccrine Sweat Glands 16.6 Conclusions References 17: Aquaporins in Fetal Development 17.1 The Water Transport across the Human Placenta 17.2 Expression of AQPs in Placental and Fetal Membranes throughout Pregnancy 17.3 Expression of AQPs in Fetal Tissues 17.3.1 Fetal Kidneys 17.3.2 Fetal Urinary Tract 17.3.3 Fetal Lungs 17.3.4 Fetal Heart 17.3.5 Fetal Skin 17.3.6 Fetal Brain 17.4 Physiological and Pathological Significance of AQPs in Fetal Membranes 17.5 Physiological and Pathological Significance of AQPs in Human Trophoblast 17.6 Regulation of AQPs in Human Fetal Membranes and Trophoblast Cells 17.6.1 Fetal Membranes 17.6.1.1 cAMP 17.6.1.2 Osmotic Stress 17.6.1.3 Insulin 17.6.1.4 Retinoic Acid 17.6.2 Trophoblast Cells 17.6.2.1 Oxygen 17.6.2.2 hCG 17.6.2.3 Vasopressin 17.6.2.4 Leptin 17.6.2.5 Insulin 17.6.2.6 TNF-α 17.6.2.7 CFTR 17.6.2.8 pH 17.6.2.9 Caveola/Caveolin-1 17.7 Conclusion References 18: Aquaporins in Diabetes Insipidus 18.1 Diabetes Insipidus 18.2 Central Diabetes Insipidus and Vasopressin 18.3 Gestational Diabetes Insipidus 18.4 Nephrogenic Diabetes Insipidus 18.4.1 Congenital Nephrogenic Diabetes Insipidus 18.4.2 Acquired Nephrogenic Diabetes Insipidus 18.4.3 VP-V2R/AQP2 Axis in Regulating Water Transport 18.5 Clinical Manifestation, Diagnosis, and Treatment of Diabetes Insipidus 18.5.1 Clinical Manifestation of Diabetes Insipidus 18.5.2 Differential Diagnosis of Diabetes Insipidus 18.5.3 Treatment of Diabetes Insipidus 18.5.4 Treatment of Central Diabetes Insipidus 18.5.5 Treatment for Nephrogenic DI 18.5.6 Novel Therapeutic Strategy for NDI 18.5.6.1 Phosphodiesterase Inhibitors 18.5.6.2 Statins 18.5.6.3 Prostaglandins 18.5.6.4 Metformin References 19: Aquaporins in Edema 19.1 Introduction 19.2 AQPs and Edema 19.2.1 Congestive Heart Failure 19.2.2 AQPs and Hepatic Cirrhosis 19.2.3 AQPs and Syndrome of Inappropriate Secretion of Antidiuretic Hormone 19.3 Conclusion References 20: Aquaporins in Obesity 20.1 Introduction 20.2 Adipose Biology and Pathophysiology 20.3 Aquaporins in Obesity 20.4 Glycerol Metabolism and Energy Homeostasis 20.5 Aquaporins in Adipose Tissue 20.5.1 AQP7 Expression and Role in Fat Accumulation 20.5.2 Regulation of AQP7 Expression 20.5.3 Other Aquaporins in Adipose Tissue 20.6 Aquaporins as Drug Targets of Obesity 20.7 Final Considerations References 21: Aquaporins in Tumor 21.1 Introduction 21.2 AQPs in Tumor 21.2.1 Water-Selective Aquaporins 21.2.1.1 AQP1 21.2.1.2 AQP2 21.2.1.3 AQP4 21.2.1.4 AQP5 21.2.1.5 AQP6 21.2.1.6 AQP8 21.2.2 Aquaglyceroporins 21.2.2.1 AQP3 21.2.2.2 AQP7 21.2.2.3 AQP9 21.2.3 Super Aquaporins 21.3 Conclusion and Prospect References 22: Aquaporin Inhibitors 22.1 Introduction 22.2 Methods for Screening AQP Inhibitors 22.2.1 Cell Swelling Assay 22.2.2 Cell Shrinking Assay 22.2.3 Stopped-Flow Assay 22.3 AQPs Inhibitors 22.3.1 Metal-Related Inhibitors 22.3.2 Proposed Quaternary Ammonium Salts 22.3.3 Small Molecules 22.3.3.1 Sulfanilamide Analogies 22.3.3.2 TGN-020 22.3.3.3 Antiepileptic Drugs 22.3.3.4 Other Compounds 22.4 Summary and Prospect References 23: Non-Aquaporin Water Channels 23.1 Introduction 23.2 Urea Transporter B 23.3 Cystic Fibrosis Transmembrane Conductance Regulator 23.4 Cotransporters 23.4.1 K-Cl Cotransporter 23.4.2 Na-K-Cl Cotransporters 23.4.3 Moncarboxylate Transporter 23.4.4 GABA Transporter 23.4.5 Na+-Coupled Glutamate Transporter EAAT 23.4.6 Sodium Glucose Transporters (SGLT) 23.4.7 Sodium Borate Cotransporter 23.4.8 Na+-Dicarboxylate Cotransporter 23.4.9 Glucose Transporter (GLUT) References 24: Methods to Measure Water Permeability 24.1 Introduction 24.2 Water Permeability Methods Based on Cell Volume Measurements 24.2.1 Water Permeability Measurement by 2D Image Analysis 24.2.2 Water Permeability Measurement by Scanning Probe Microscopy 24.2.3 Water Permeability Measurement by Light Scattering and Spatial Filtering Microscopy 24.2.4 Water Permeability Measurement by Bioelectrical Impedance Analysis 24.2.5 Water Permeability Measurement by Digital Holographic Microscopy 24.2.6 Water Permeability Measurement by Microfluidic-Based Methods 24.3 Water Permeability Methods for In Vivo and Ex Vivo Studies 24.4 Conclusion References Index