Interdisciplinarity is more often invoked than practised. This is hardly surprising, considering the daunting vastness of modern biology. To reach a satisfactory understanding of a complex biological system, a wide spectrum of conceptual and experimental tools must be applied at different levels, from the molecular to the cellular, tissue and organismic. We believe the multifaceted regulatory interplay between integrin receptors and ion channels offers a rich and challenging field for researchers seeking broad biological perspectives. By mediating cell adhesion to the extracellular matrix, integrins regulate many developmental processes in the widest sense (from cell choice between differentiation and proliferation, to tissue remodeling and organogenesis). Rapidly growing evidence shows that frequent communication takes place between cell adhesion receptors and channel proteins. This may occur through formation of multiprotein membrane complexes that regulate ion fluxes as well as a variety of intracellular signaling pathways. In othercases, cross talk is more indirect and mediated by cellular messengers such as G proteins. These interactions are reciprocal, in that ion channel stimulation often controls integrin activation or expression. From a functional standpoint, studying the interplay between integrin receptors and ion channels clarifies how the extracellular matrix regulates processes as disparate as muscle excitability, synaptic plasticity and lymphocyte activation, just to mention a few. The derangement of these processes has many implications for pathogenesis processes, in particular for tumor invasiveness and some cardiovascular and neurologic diseases. This book provides a general introduction to the problems and methods of this blossoming field.
This book explores the multifaceted regulatory interplay between integrin receptors and ion channels. The essays here explain how the extracellular matrix regulates processes as disparate as muscle excitability, synaptic plasticity and lymphocyte activation.
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Integrin Structure and Functional Relation with Ion Channels |
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1 | (8) |
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1 | (1) |
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1 | (1) |
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Fundamentals of Integrin Structure |
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2 | (3) |
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Physiological and Pathological Implications: An Outline of Current Trends |
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5 | (1) |
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6 | (3) |
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Introduction to Ion Channels |
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9 | (14) |
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9 | (1) |
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9 | (1) |
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The Physiology of Ion Channels |
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10 | (3) |
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Ion Channel Types Involved in Integrin-Mediated Signaling |
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13 | (6) |
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19 | (4) |
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Biochemical Methods to Study the Interactions Between Integrins and Ion Channels |
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23 | (10) |
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23 | (1) |
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24 | (1) |
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Yeast Two-Hybrid Screening |
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24 | (2) |
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Affinity-Based Screening: IP Assays |
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26 | (1) |
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27 | (1) |
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Photoaffinity Labeling Techniques for Studying Transient Protein-Protein Interaction |
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28 | (1) |
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Far Western Blot Analysis (Far WB) |
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29 | (1) |
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High-Throughput Protein-Protein Interaction Analysis, Followed by Validation of Candidate Interactors through Different Experimental Approaches |
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29 | (1) |
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30 | (3) |
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Optical Methods in the Study of Protein-Protein Interactions |
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33 | (10) |
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33 | (1) |
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34 | (1) |
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Forster Resonance Energy Transfer: The "Molecular Ruler" |
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34 | (2) |
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Intensity Versus Lifetime: Two Ways to Measure FRET |
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36 | (2) |
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Total Internal Reflection Fluorescence Microscopy (TIRFM) and Imaging of Membrane Proteins |
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38 | (1) |
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Antibody-Based Versus Fusion Protein-Based FRET: Principles |
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38 | (1) |
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Antibody-Based Versus Fusion Protein-Based FRET: Advantages and Disadvantages |
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39 | (1) |
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Application of Optical Methods to the Study of Integrins and Ion Channels |
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40 | (1) |
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41 | (2) |
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Integrins and Signal Transduction |
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43 | (12) |
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Maria del Pilar Camacho Leal |
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43 | (1) |
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Overview of Integrin Structure |
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43 | (3) |
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The SFK-Fak-p130Cas Signaling |
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46 | (6) |
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52 | (3) |
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Physical and Functional Interaction Between Integrins and Herg1 Channels in Cancer Cells |
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55 | (14) |
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55 | (1) |
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56 | (1) |
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hERG1 Channels in Cancer Cells |
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56 | (3) |
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Effects of Integrin Activation on hERG1 Channels |
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59 | (2) |
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Integrins and hERG1 Channels form a Macromolecular Complex |
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61 | (1) |
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Effects of hERG1 Activation on Integrin Function and Signaling |
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62 | (2) |
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64 | (5) |
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Coordinated Regulation of Vascular CA2+ and K+ Channels by Integrin Signaling |
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69 | (12) |
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69 | (1) |
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69 | (1) |
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Regulation of L-Type Calcium Channels by Integrin Activation |
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70 | (3) |
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Regulation of Ca2+Dependent Potassium Channels by Integrin Activation |
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73 | (3) |
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76 | (5) |
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Adhesion-Dependent Modulation of Macrophage K+ Channels |
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81 | (14) |
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Margaret Colden-Stanfield |
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81 | (1) |
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81 | (1) |
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Inwardly Rectifying K+ (Kir) Currents |
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81 | (6) |
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Physiologic and Pathophysiologic Roles of Macrophage Kir Channels |
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87 | (1) |
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Delayed, Outwardly Rectifying K+ (Kdr) Currents |
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88 | (1) |
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Physiologic and Pathophysiologic Roles of Macrophage Kdr Channels |
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89 | (3) |
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92 | (3) |
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Integrin Receptors and Ligand-Gated Channels |
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95 | (12) |
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95 | (1) |
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95 | (1) |
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The Functional Significance of Integrins in the Adult Brain |
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96 | (4) |
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Integrins and Nicotinic Acetylcholine Receptors: Not Only the Neuromuscular Junction |
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100 | (2) |
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102 | (5) |
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Integrins and Ion Channels in Cell Migration: Implications for Neuronal Development, Wound Healing and Metastatic Spread |
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107 | (18) |
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107 | (1) |
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108 | (2) |
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The Role of Integrins in Cell Migration |
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110 | (1) |
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The Role of Ion Channels and Crosstalk with Integrins in Cell Migration |
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111 | (2) |
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Ca2+ Signaling and the Axonal Growth Cone |
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113 | (2) |
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Ion Channels as Adhesion Molecules |
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115 | (1) |
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The Cellular Environment and the Metastatic Process |
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115 | (3) |
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Invasiveness of Glial Tumors and Ion Channels |
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118 | (1) |
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118 | (7) |
Index |
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125 | |
ANDREA BECCHETTI, PhD, is Professor of General, Comparative and Cellular Physiology at the Department of Biotechnology and Biosciences of the University of Milano-Bicocca, Italy. After receiving his academic degrees at the University of Milan, he has spent prolonged research sojourns at the Department of General Pathology of the University of Florence, Italy, the Department of Physiology at Emory University in Atlanta, Georgia, USA, the Department of Physiological Sciences of the University of Newcastle upon Tyne, UK, and the Biophysics Sector of the International School for Advanced Studies (ISAS-SISSA), in Trieste, Italy. His current research interests include the role of ion channels in cell adhesion and proliferation, the nicotinic modulation of synaptic transmission in the mammalian cerebral cortex and the pathogenesis of sleep-related epileptic forms linked to mutant human nicotinic receptors. Andrea Becchetti is member of the Society of General Physiologists, Biophysical Society, Society for Neuroscience and the Italian Physiological Society.
ANNAROSA ARCANGELI, MD, PhD is Professor of General Pathology and Immunology at the Department of Experimental Pathology and Oncology of the University of Firenze (Florence, Italy). She is the Scientific Director of the Laboratory of Genetic Engineering for the Production of Animal Models of the University of Firenze. After receiving her MD degree at the University of Firenze, she spent several research sojourns at the Department of Physiology of the University of Milano, at the Institut dEmbriologie Cellulaire et Moleculaire, Nogent sur Marne, Paris, France and at the MRC-LMB Centre of Cambridge, UK. Her main research interests include the role of ion channels, in particular potassium channels, in the regulation of different aspects of tumor cell behaviour, including the cross talk with adhesion receptors, as well as the identification of ion channels as novel targetsfor cancer therapy. Annarosa Arcangeli is member of the Italian Society of Pathology, the Association of Cell Biology and Differentiation (ABCD), the American Society of Hematology.