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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.
Integrins are heterodimeric cell surface receptors which anchor cells to different extracellular matrix proteins or act as cell-cell receptors. They play pivotal roles not only across a wide range of physiological processes including tissue morphogenesis, wound healing, and regulation of cell growth, but also in numerous pathological conditions such as autoimmunity, infectious disease, and carcinogenesis. This book aims to provide readers a summary of the most important integrins and their respective biological functions. Readers will learn about knockout- and animal models to study the functionality of key collagen-, laminin-, and nephronectin-binding integrins. Additionally, the role of integrins in pathological tissue remodeling in joints and in developing and diseased cardiac tissue are discussed. Reviews of the current knowledge of the role of integrins in tissue and tumor fibrosis, angiogenesis and tumor progression are an important part of this work. Finally, the book discusses integrins in the context of the immune system, how to target integrin-ligand interactions with antibodies, and the role of integrins as receptors for bacterial and viral cell invasion. Both experienced researchers and clinicians, as well as PhD students who wish to study the extracellular matrix and cell adhesion molecules will find “Integrins in Health and Disease - Key Effectors of Cell-Matrix and Cell-Cell Interactions” authoritative, easily accessible, and vastly informative. The series Biology of Extracellular Matrix is published in collaboration with the American Society for Matrix Biology and the International Society for Matrix Biology.
Integrins: Molecular and Biological Responses to the Extracellular Matrix will help basic, applied, and clinical researchers keep up with the explosion of literature on the integrin family of proteins. This volume extends material previously covered in Receptors for Extracellular Matrix. It addresses some of the most exciting areas of integrin biology, including the varied roles of integrins in cell division, differentiation, movement, wound healing, inflammation, thrombosis, osteoporosis, and cancer. Describes key aspects of integrin structure, function, and biology Covers collagen receptors, epithelial cell integrins, leukocyte integrins, platelet integrins, integrin signaling, and integrin antagonists Investigates the expression and role of integrins during development and in the cytoskeleton Includes the actions and influences of integrins in inflammation, thrombosis, and osteoporosis
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.
In conclusion, this work provided new insights into the kinetic mechanism of integrin-mediated leukocyte rolling and firm adhesion, but also a mechanism for lymphocyte homing through the unique ligand-specific regulation of integrin adhesion by different chemokines. Our findings are also fundamental to understanding integrin-GPCR transactivation, and Hantavirus pathogenesis.
This volume provides the most cutting edge technologies related to the study of integrin activation and the characterization of their vast interactomes. Chapters detail protocols on experimental approached to quantify focal adhesion parameters, integrin activation, and the lateral interaction of integrins with transmembrane binding partners. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, The Integrin Interactome: Methods and Protocols aims to give the reader a multi-scale journey from single bonds inside protein structures to the function of these crucial adhesion receptors at a whole organism level in physiology and pathology.