Fibronectins / Edition 1

by Richard O. Hynes

Overview

Fibronectins comprise a class of high molecular weight glycoproteins present both in extracellular matrices and in soluble form in body fluids. Although they have been studied for about forty years, their real significance emerged only during the past decade. Intensive research has focused on their role in platelet function, cell migration, the cytoskeleton, reticuloendothelial function, and on alterations in fibronectin distribution during development and disease. Fibronectins have emerged as glycoproteins with a very interesting set of properties generally involving adhesion of cells to cells or to extracellular material. In more recent years, the complete sequences of several fibronectin molecules and their genes were determined, the relation between structure and function was understood and much has been learned about cell surface receptors for fibronectins and other adhesive ligands. Having been at the forefront of all these exciting developments, the author has synthesized the entire field and with all the latest information at hand for the first time given it a clear perspective.

Product Details

ISBN-13:	9781461279402
Publisher:	Springer New York
Publication date:	09/27/2011
Series:	Springer Series in Molecular and Cell Biology
Edition description:	Softcover reprint of the original 1st ed. 1990
Pages:	546
Product dimensions:	6.10(w) x 9.25(h) x 0.05(d)

Table of Contents

1. Introduction and Historical Overview.- 1.1 Beginnings: 1948–1976.- 1.2 Development: 1975–1977.- 1.3 An Expanding Field: 1978–1982.- 1.4 The Impact of Molecular Biology: 1983–1988.- 2. Methods for Identification of Fibronectins.- 2.1 Definitions.- 2.2 Purification of Fibronectins.- 2.3 Preparation of Antibodies.- 2.4 Immunofluorescence and Immunoperoxidase Staining.- 2.5 Immunoprecipitation.- 2.6 Radioimmunoassay (RIA) and Enzyme Immunoassay (ELISA).- 2.7 Other Immunological Assays.- 2.8 Surface Labeling of Cells.- 3. Distribution of Fibronectins in Vivo.- 3.1 Phylogenetic Distribution of Fibronectins.- 3.1.1 Mammals and Birds.- 3.1.2 Amphibians, Fish, and Reptiles.- 3.1.3 Invertebrates.- 3.2 Fibronectins of Body Fluids.- 3.2.1 Plasma.- 3.2.2 Amniotic Fluid.- 3.2.3 Bronchoalveolar Lavage Fluid.- 3.2.4 Synovial Fluid.- 3.2.5 Cerebrospinal Fluid.- 3.2.6 Seminal Plasma.- 3.2.7 Other Body Fluids.- 3.3 Distribution of Fibronectin in Matrices in Vivo.- 3.3.1 Technical Aspects.- 3.3.2 Immunolocalization of Fibronectin.- 3.3.3 Basal Lamina or Basement Membrane?.- 3.3.4 Fibronectin in the Kidney.- 3.3.5 Conclusions.- 4. Expression of Fibronectins by Cells in Culture.- 4.1 General Comments and Experimental Criteria.- 4.2 Fibroblasts.- 4.3 Mesenchymal Cells.- 4.4 Chondrocytes.- 4.5 Myoblasts and Myotubes.- 4.6 Smooth and Cardiac Muscle Cells.- 4.7 Endothelial Cells.- 4.8 Platelets.- 4.9 Neutrophils.- 4.10 Macrophages.- 4.11 Neural Crest Cells.- 4.12 Astrocytes.- 4.13 Schwann Cells.- 4.14 Neurons and Neuroblastomas.- 4.15 Hepaytes.- 4.16 Kidney Cells.- 4.17 Mammary Gland Cells.- 4.18 Amniotic Epithelial Cells.- 4.19 Keratinocytes.- 4.20 Other Epithelial Cells.- 4.21 Teraarcinoma Cells and Their Derivatives.- 5. Interactions of Fibronectins.- 5.1 Gelatin and Collagen.- 5.2 Fibrin and Fibrinogen.- 5.3 Factor XHIa and Other Transglutaminases.- 5.4 Glycosaminoglycans and Proteoglycans.- 5.5 Gangliosides and Phospholipids.- 5.6 Actin and Other Cytoskeletal Proteins.- 5.7 DNA.- 5.8 Clq Component of Complement.- 5.9 Amyloid P and C-Reactive Protein.- 5.10 Acetylcholinesterase.- 5.11 Thrombospondin.- 5.12 Conclusions.- 6. Structure of Fibronectins.- 6.1 Overview.- 6.2 Fragmentation and Location of Binding Sites.- 6.2.1 The N-Terminal Domain.- 6.2.2 The Gelatin-Binding Domain.- 6.2.3 The Central Region of the Molecule.- 6.2.4 The Cell-Binding Domain.- 6.2.5 The High-Affinity Heparin-Binding Domain.- 6.2.6 The C-Terminal Fibrin-Binding Domain.- 6.2.7 The C-Terminal Interchain Disulfide Bonds.- 6.2.8 Conclusion.- 6.3 Primary Structure.- 6.3.1 General Features.- 6.3.2 The N-Terminal Domain: Type I Homologies.- 6.3.3 The Gelatin-Binding Domain: Type I and Type II Homologies.- 6.3.4 The C-Terminal Region: More Type I Homologies.- 6.3.5 The Type III Central Region.- 6.3.6 The Leader Sequence of FN.- 6.3.7 Conclusions, Speculations, and Future Directions.- 6.4 A Single Fibronectin Gene Encodes Multiple Fibronectins.- 6.4.1 Exon-Intron Structure.- 6.4.2 The Promoter and Terminator Regions.- 6.4.3 Alternative Splicing.- 6.4.4 Different Forms of Fibronectin Arise by Alternative Splicing.- 6.4.5 Possible Functions of Variable Segments.- 6.5 Post-Translational Modifications.- 6.5.1 Glycosylation.- 6.5.2 Phosphorylation and Sulfation.- 6.6 Secondary and Tertiary Structure.- 6.6.1 Overall Conformation.- 6.6.2 Secondary Structure.- 6.6.3 Domain Structure of Fibronectin.- 6.6.4 Effects of Interactions with Other Components.- 6.7 Conclusions.- 7. Biosynthesis and Fibrillogenesis.- 7.1 Kinetics of Synthesis and Glycosylation.- 7.2 Disulfide Bonding.- 7.3 Composition of the Extracellular Matrix.- 7.3.1 Other Glycoproteins and Collagens.- 7.3.2 Proteoglycans.- 7.3.3 Ultrastructure of the Matrix.- 7.4 Matrix Formation and Structure.- 7.4.1 In Vitro Analyses.- 7.4.2 In Situ Analyses.- 7.4.3 The Role of the Cells.- 7.5 Regulation of Levels of Fibronectin.- 7.5.1 Culture Conditions.- 7.5.2 Polypeptide Growth Factors: EGF and TGF-ß.- 7.5.3 Interferon.- 7.5.4 Steroid and Thyroid Hormones.- 7.5.5 Cyclic Nucleotides.- 7.5.6 Conclusion.- 8. Cellular Adhesion and Cell Surface Receptors.- 8.1 Fibronectin Binding to Substrata.- 8.2 Attachment and Spreading of Cells on Fibronectin.- 8.3 Role of Other Molecules in Cellular Adhesion.- 8.4 Role of Fibronectin in Later Steps of Cellular Adhesion.- 8.4.1 Multiple Cell-Binding Sites in Fibronectin.- 8.5 Cell Surface Receptors for Fibronectin.- 8.5.1 Evidence for a Role of Glycoproteins.- 8.5.2 Integrins: A Family of Cell Surface Receptors.- 8.5.3 Evidence for a Role of Gangliosides.- 8.5.4 Evidence for a Role of Proteoglycans.- 8.5.5 Conclusions and Speculations.- 9. Fibronectin and the Cytoskeleton.- 9.1 Correlations and Reciprocal Effects.- 9.2 Microscopic Evidence.- 9.2.1 Codistribution of FN and Actin.- 9.2.2 Codistribution of Other Cytoskeletal Proteins.- 9.2.3 Fibronectin Associated with Focal Contacts and/or Attachment Plaques.- 9.3 Integrins and the Transmembrane Connection.- 10. Cell Migration.- 10.1 Fibronectin and Cell Migration in Vitro.- 10.2 Fibronectin and Cell Migration in Embryos.- 10.2.1 Avian Gastrulation.- 10.2.2 Amphibian Gastrulation.- 10.2.3 Echinoderm Gastrulation.- 10.2.4 Early Mammalian Embryos.- 10.2.5 Neural Crest Migration.- 10.2.6 Area Vasculosa.- 10.2.7 Primordial Germ Cells.- 10.2.8 Eye Development.- 10.2.9 Cardiac Development.- 10.2.10 Neurite Outgrowth.- 10.3 Fibronectin and the Logic of Cell Migration.- 10.3.1 Directionality and Vectors.- 10.3.2 Barriers to Migration and Choice of Pathways.- 10.3.3 Origin of Pathways.- 10.3.4 Initiation and Termination of Migration.- 11. Development and Differentiation.- 11.1 Morphogenesis.- 11.1.1 Gastrulation.- 11.1.2 Neurulation and Somitogenesis.- 11.1.3 Formation of Organs via Epithelial-Mesenchymal Interactions.- 11.1.4 Potential Functions for FN in Morphogenetic Processes.- 11.1.5 Limb Bud Development.- 11.2 Differentiation and Growth.- 11.2.1 Chondrogenesis and Osteogenesis.- 11.2.2 Myogenesis.- 11.2.3 Adipogenesis and Steroidogenesis.- 11.2.4 Hematopoiesis.- 11.2.5 Proliferation and Differentiation.- 11.3 Conclusion.- 12. Oncogenic Transformation.- 12.1 Altered FN Expression.- 12.1.1 Loss of FN from Virally Transformed Cells in Vitro.- 12.1.2 Expression of FN by Other Transformed Cells in Vitro.- 12.1.3 Effects of Phorbol Esters.- 12.1.4 Distribution of FN in Tumors in Vivo.- 12.1.5 Effects of Tumors on FN Levels in Plasma and Elsewhere.- 12.1.6 Correlations between Fibronectin Expression in Vitro and Tumor Development in Vivo.- 12.1.7 Conclusions.- 12.2 Phenotypic Consequences of Altered FN Expression.- 12.2.1 Restoration of FN to Transformed Cells.- 12.3 Possible Mechanisms of Loss of FN.- 12.3.1 Alterations in Biosynthetic Rate.- 12.3.2 Alternative Splicing of FN mRNA.- 12.3.3 Posttranslational Modifications.- 12.3.4 Transformation-Induced Proteolysis.- 12.3.5 Effects on the Cytoskeleton.- 12.3.6 Alterations in Integrins.- 12.3.7 Conclusions.- 13. Hemostasis and Thrombosis.- 13.1 Fibronectin and Platelets.- 13.1.1 Occurrence.- 13.1.2 Release and Binding of Fibronectin.- 13.1.3 Receptors for FN on Platelet Cell Surfaces.- 13.1.4 Functional Roles of Fibronectin.- 13.1.5 Potential for Clinical Application.- 13.2 Fibronectin in Blood Clots.- 14. Wound Healing, Inflammation, and Fibrosis.- 14.1 Wound Healing.- 14.1.1 Cutaneous Wound Healing.- 14.1.2 Corneal Wound Healing.- 14.1.3 Therapeutic Treatments with Fibronectin.- 14.2 Inflammation and Fibrosis.- 14.2.1 Fibrosis of the Lung.- 14.2.2 Fibronectin in Arthritis.- 14.2.3 Proliferative Vitreoretinopathy.- 14.3 Conclusions and Future Prospects.- 15. Phagocytosis and Interactions with Pathogenic Microorganisms.- 15.1 Role of Fibronectin in Phagocytosis.- 15.2 Fibronectin Binding to Microorganisms.- 15.2.1 Staphylococci.- 15.2.2 Strepocci.- 15.2.3 Gram-Negative Bacteria.- 15.2.4 Treponema pallidum (Syphilis).- 15.2.5 Yeasts.- 15.2.6 Parasitic Protozoa.- 15.2.7 Is FN Binding to Microorganisms Advantageous or Disadvantageous?.- 15.3 Plasma Fibronectin, Reticuloendothelial Function, Trauma, and Sepsis.- 15.3.1 Is pFN a Nonspecific Opsonin?.- 15.3.2 What Are the Implications of Fluctuations in pFN Levels?.- 15.3.3 Is pFN Injection an Effective Therapy?.- 15.3.4 Conclusions.- 16. Implications for Future Research.- 16.1 Molecular Issues.- 16.2 Cellular Issues.- 16.3 Issues of Developmental Biology.- 16.4 Issues of Physiology and Pathology.- References.