An integrin, or integrin receptor, is an integral membrane protein in the plasma membrane of cells. It plays a role in the attachment of a cell to the extracellular matrix (ECM) and to other cells, and in signal transduction from the ECM to the cell. There are many types of integrin, and many cells have multiple types on their surface. Integrins are of vital importance to all metazoans, from humans to sponges. This volume in Methods in Enzymology presents methods for studying integrins.

Cell adhesion is essential for the organization of multicellular organisms. Indeed, various types of cell adhesion receptors, including cadherins and integrins, are present in animals ranging from nematodes and insects to vertebrates. In this book, we focus on the integrin family, which is shared among all metazoans, but has expanded considerably with vertebrate evolution. Since the cloning of the first integrin subunit, some twenty years ago, integrin biology has been-and still is-a topic of intense study. Integrin-mediated adhesion is a regulated process that, in turn, regulates the organization of the actin cytoskeleton. Moreover, it has become clear from in vitro analyses that integrin-mediated adhesion can affect virtually all aspects of cellular behavior-including polarity, motility, proliferation, survival, and differentiation. This book aims to provide an extensive overview of the current knowledge about the regulation of developmental processes as well as the maintenance of proper tissue function, by integrin-mediated adhesion. In addition, key aspects of integrin cell biology are discussed. Chapter 1 of this book is meant as an introduction in integrin biology and is followed by a more in-depth discussion of the roles that integrins play in extracellular matrix assembly, in cell migration, and in the regulation of intracellular signaling cascades (Chapters 2-4). Subsequently, Chapters 5 and 6 discuss what has been learned about the role of integrins and associated proteins in animal development from genetic analysis of two invertebrates- the flatworm, C. elegans and the fruit fly, D. melanogaster. The relatively limited number of genes encoding adhesion-related proteins and the relative ease and speed with which genetic experiments can be performed in these animals, have allowed researchers to study the basic principles of integrin biology in vivo. Finally, Chapters 7-14 discuss how integrin-mediated adhesion regulates the development and functionality of the different mammalian organ systems, based to a large extent on (conditional) gene knockout studies in mice and on studies in human patients.

This updated edition is a comprehensive treatise that spans the complete range of basic biochemistry of bone and cartilage components to the clinical evaluation of disease markers in bone and joint disorders. With contributions from over 75 international experts, Dynamics of Bone and Cartilage Metabolism, Second Edition, is indispensable reading for those involved in skeletal research as well as for rheumatologists, endocrinologists, clinical biochemists, and other clinical disciplines participating in the management of patients with bone and cartilage diseases. - Part I provides an up-to-date account of current knowledge of the structure, biosynthesis and molecular biology of the major tissue components - Part II covers the organizational structure and cellular metabolism of bone and cartilage - Part III deals with the utility of components specific to bone and cartilage as biomarkers of health and disease

Cell adhesion is essential for the organization of multicellular organisms. Indeed, various types of cell adhesion receptors, including cadherins and integrins, are present in animals ranging from nematodes and insects to vertebrates. In this book, we focus on the integrin family, which is shared among all metazoans, but has expanded considerably with vertebrate evolution. Since the cloning of the first integrin subunit, some twenty years ago, integrin biology has been—and still is—a topic of intense study. Integrin-mediated adhesion is a regulated process that, in turn, regulates the organization of the actin cytoskeleton. Moreover, it has become clear from in vitro analyses that integrin-mediated adhesion can affect virtually all aspects of cellular behavior—including polarity, motility, proliferation, survival, and differentiation. This book aims to provide an extensive overview of the current knowledge about the regulation of developmental processes as well as the maintenance of proper tissue function, by integrin-mediated adhesion. In addition, key aspects of integrin cell biology are discussed. Chapter 1 of this book is meant as an introduction in integrin biology and is followed by a more in-depth discussion of the roles that integrins play in extracellular matrix assembly, in cell migration, and in the regulation of intracellular signaling cascades (Chapters 2-4). Subsequently, Chapters 5 and 6 discuss what has been learned about the role of integrins and associated proteins in animal development from genetic analysis of two invertebrates— the flatworm, C. elegans and the fruit fly, D. melanogaster. The relatively limited number of genes encoding adhesion-related proteins and the relative ease and speed with which genetic experiments can be performed in these animals, have allowed researchers to study the basic principles of integrin biology in vivo. Finally, Chapters 7-14 discuss how integrin-mediated adhesion regulates the development and functionality of the different mammalian organ systems, based to a large extent on (conditional) gene knockout studies in mice and on studies in human patients.

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 other cases, 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.

The integrin family is composed of 24 members and approximately ten years ago (2003) we published a book devoted to the nine I domain integrin subunits. In this second edition, I am pleased that most of the original authors have been able to contribute to the updated version. I domain containing integrins include collagen receptors and leukocyte receptors. In 2003 the knockout mouse phenotypes for all of the I domain integrins had not yet been published; they are now, and are summarized and discussed in this edition. Interestingly, a recent 10 integrin mutation in dogs has indicated that collagen-binding integrins in the musculoskeletal system might have much more severe phenotypes in larger animals/humans compared to the mild integrin phenotypes observed in collagen-binding integrin deficient mice. This finding is further discussed in the book. In the cancer field, the microenvironment is taking center stage, and here collagen receptors on fibroblasts are predicted to play important roles in paracrine signaling, in regulating tissue stiffness and matrix remodeling. New technologies, new mouse models in combination with analyses of I integrins in larger animals/humans are thus predicted to increase our knowledge about this group of receptors. With this in mind we look forward to another 10 years of research with I domain integrins.

Cells in the developing embryo depend on signals from the extracellular environment to help guide their differentiation. An important mediator in this process is the extracellular matrix – secreted macromolecules that interact to form large protein networks outside the cell. During development, the extracellular matrix serves to separate adjacent cell groups, participates in establishing morphogenic gradients, and, through its ability to interact directly will cell-surface receptors, provides developmental clocks and positional information. This volume discusses how the extracellular matrix influences fundamental developmental processes and how model systems can be used to elucidate ECM function. The topics addressed range from how ECM influences early development as well as repair processes in the adult that recapitulate developmental pathways.

This book explores the latest data dealing with mechanosensitive channels research results. It was compiled by a group of internationally recognized scientists leading in the field of mechanosensitive ion channels or mechanically gated channels and signaling cascades research. Key problems of cell mechanobiology are also discussed. As a whole, the volume dwells on the major issues of mechanical stress influencing the ion channels and intracellular signaling pathways.

with contributions by numerous experts