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E-raamat: Integrins and Ion Channels: Molecular Complexes and Signaling

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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.
Integrin Structure and Functional Relation with Ion Channels
1(8)
Annarosa Arcangeli
Andrea Becchetti
Abstract
1(1)
Introduction
1(1)
Fundamentals of Integrin Structure
2(3)
Physiological and Pathological Implications: An Outline of Current Trends
5(1)
Conclusion
6(3)
Introduction to Ion Channels
9(14)
Chiara Di Resta
Andrea Becchetti
Abstract
9(1)
Introduction
9(1)
The Physiology of Ion Channels
10(3)
Ion Channel Types Involved in Integrin-Mediated Signaling
13(6)
Conclusion
19(4)
Biochemical Methods to Study the Interactions Between Integrins and Ion Channels
23(10)
Olivia Crociani
Abstract
23(1)
Introduction
24(1)
Yeast Two-Hybrid Screening
24(2)
Affinity-Based Screening: IP Assays
26(1)
Pull-Down Assay
27(1)
Photoaffinity Labeling Techniques for Studying Transient Protein-Protein Interaction
28(1)
Far Western Blot Analysis (Far WB)
29(1)
High-Throughput Protein-Protein Interaction Analysis, Followed by Validation of Candidate Interactors through Different Experimental Approaches
29(1)
Conclusion
30(3)
Optical Methods in the Study of Protein-Protein Interactions
33(10)
Alessio Masi
Riccardo Cicchi
Adolfo Carloni
Francesco Saverio Pavone
Annarosa Arcangeli
Abstract
33(1)
Introduction
34(1)
Forster Resonance Energy Transfer: The "Molecular Ruler"
34(2)
Intensity Versus Lifetime: Two Ways to Measure FRET
36(2)
Total Internal Reflection Fluorescence Microscopy (TIRFM) and Imaging of Membrane Proteins
38(1)
Antibody-Based Versus Fusion Protein-Based FRET: Principles
38(1)
Antibody-Based Versus Fusion Protein-Based FRET: Advantages and Disadvantages
39(1)
Application of Optical Methods to the Study of Integrins and Ion Channels
40(1)
Conclusion
41(2)
Integrins and Signal Transduction
43(12)
Sara Cabodi
Paola Di Stefano
Maria del Pilar Camacho Leal
Agata Tinnirello
Brigitte Bisaro
Virginia Morello
Laura Damiano
Simona Aramu
Daniele Repetto
Giusy Tornillo
Paola Defilippi
Abstract
43(1)
Overview of Integrin Structure
43(3)
The SFK-Fak-p130Cas Signaling
46(6)
Conclusion
52(3)
Physical and Functional Interaction Between Integrins and Herg1 Channels in Cancer Cells
55(14)
Serena Pillozzi
Annarosa Arcangeli
Abstract
55(1)
Introduction
56(1)
hERG1 Channels in Cancer Cells
56(3)
Effects of Integrin Activation on hERG1 Channels
59(2)
Integrins and hERG1 Channels form a Macromolecular Complex
61(1)
Effects of hERG1 Activation on Integrin Function and Signaling
62(2)
Conclusion
64(5)
Coordinated Regulation of Vascular CA2+ and K+ Channels by Integrin Signaling
69(12)
Peichun Gui
Jun-Tzu Chao
Xin Wu
Yan Yang
George E. Davis
Michael J. Davis
Abstract
69(1)
Introduction
69(1)
Regulation of L-Type Calcium Channels by Integrin Activation
70(3)
Regulation of Ca2+Dependent Potassium Channels by Integrin Activation
73(3)
Conclusion
76(5)
Adhesion-Dependent Modulation of Macrophage K+ Channels
81(14)
Margaret Colden-Stanfield
Abstract
81(1)
Introduction
81(1)
Inwardly Rectifying K+ (Kir) Currents
81(6)
Physiologic and Pathophysiologic Roles of Macrophage Kir Channels
87(1)
Delayed, Outwardly Rectifying K+ (Kdr) Currents
88(1)
Physiologic and Pathophysiologic Roles of Macrophage Kdr Channels
89(3)
Conclusion
92(3)
Integrin Receptors and Ligand-Gated Channels
95(12)
Raffaella Morini
Andrea Becchetti
Abstract
95(1)
Introduction
95(1)
The Functional Significance of Integrins in the Adult Brain
96(4)
Integrins and Nicotinic Acetylcholine Receptors: Not Only the Neuromuscular Junction
100(2)
Conclusion
102(5)
Integrins and Ion Channels in Cell Migration: Implications for Neuronal Development, Wound Healing and Metastatic Spread
107(18)
Andrea Becchetti
Annarosa Arcangeli
Abstract
107(1)
Introduction
108(2)
The Role of Integrins in Cell Migration
110(1)
The Role of Ion Channels and Crosstalk with Integrins in Cell Migration
111(2)
Ca2+ Signaling and the Axonal Growth Cone
113(2)
Ion Channels as Adhesion Molecules
115(1)
The Cellular Environment and the Metastatic Process
115(3)
Invasiveness of Glial Tumors and Ion Channels
118(1)
Conclusion
118(7)
Index 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.