The Collagen Superfamily and Collagenopathies (Biology of Extracellular Matrix, 8)

"This book aims at providing insights into the collagen superfamily and the remarkable diversity of collagen function within the extracellular matrix. Additionally, the mechanisms underlying collagen-related diseases such as dystrophic epidermolysis bullosa, osteogenesis imperfecta, as well as collagen-related myopathies and neurological disorders are discussed. Collagens are the most abundant extracellular matrix proteins in organisms. Their primary function is to provide structural support and strength to cells and to maintain biomechanical integrity of tissues. However, collagens can no longer be considered just as structural proteins. They can act as extracellular modulators of signaling events and serve critical regulatory roles in various cell functions during embryonic development and adult homeostasis. Furthermore, collagens are associated with a broad spectrum of heritability-related diseases known as 'collagenopathies' that affect a multitude of organs and tissues including sensorial organs. The book is a useful introduction to the field for junior scientists, interested in extracellular matrix research. It is also an interesting read for advanced scientists and clinicians working on collagens and collagenopathies, giving them a broader view of the field beyond their area of specialization." Preface Contents About the Editor Chapter 1: The Collagen Superfamily: Everything You Always Wanted to Know 1.1 Introduction 1.2 Collagens Belong to the Core Matrisome 1.3 Collagen, a Singular Protein that Should Be Read as Plural 1.4 Collagen Biosynthesis: A Complex and Multistep Process 1.5 Collagens Across Species 1.6 An Introduction to Collagenopathies 1.7 Outlook 1.8 Concluding Remarks References Chapter 2: Procollagen Trafficking and its Implications in Osteogenesis Imperfecta 2.1 Introduction 2.2 Type I Collagen and Procollagen 2.3 Collagen Trafficking Disruptions in Heritable Bone Pathology 2.3.1 Osteogenesis Imperfecta 2.3.2 Skeletal Pathology in Other Protein Trafficking Disorders 2.4 Basic Trafficking Concepts for Secretory Proteins 2.4.1 Secretory Trafficking 2.4.2 Degradative Trafficking 2.5 Procollagen Secretion 2.5.1 ER-Golgi Trafficking 2.5.2 Golgi Progression and TGN Sorting 2.6 Procollagen Degradation 2.6.1 ERAD 2.6.2 Autophagy 2.6.3 Quality Control and Sorting 2.7 Therapeutic Implications 2.8 Concluding Remarks References Chapter 3: Collagens in the Physiopathology of the Ehlers-Danlos Syndromes 3.1 The Ehlers-Danlos Syndromes and Collagen, an Intimate History 3.2 General Clinical Presentation of the Ehlers-Danlos Syndromes 3.3 Classification, Diagnostic Criteria, and Prevalence 3.4 Defects in the Primary Structure, Processing, Folding, and Cross-Linking of Fibrillar Collagens 3.4.1 Collagen I Defects 3.4.2 Collagen III Defects 3.4.3 Collagen V Defects 3.4.4 Defects in Collagen Folding and Cross-Linking 3.5 More than Collagen? Beyond the Fibrillar Collagens 3.5.1 Defects in Bridging Molecules 3.5.2 Defects in Glycosaminoglycan Biosynthesis 3.5.3 Other Proteins 3.6 Concluding Remarks References Chapter 4: Cartilage Collagens and Associated Disorders 4.1 Introduction 4.2 Defects in Structural Proteins of Cartilage 4.3 Diseases by Collagen Types 4.3.1 Collagen II 4.3.2 Collagen IX 4.3.3 Collagen XI 4.3.4 Collagen X 4.4 Outlook: Therapy References Chapter 5: Collagen IV-Related Diseases and Therapies 5.1 Introduction 5.2 Collagen IV 5.3 Gene Organisation and Regulation 5.3.1 COL4A1 and COL4A2 5.3.2 COL4A3 and COL4A4 5.3.3 COL4A5 and COL4A6 5.4 Collagen IV Protein Domain Structure and Biosynthesis 5.4.1 NC1 Domains and Initiation of Protomer Folding 5.4.2 Post-translational Modification of Collagen IV α-chains 5.4.3 Collagen Triple Helix Folding 5.4.4 Transport from the Intracellular to the Extracellular Space 5.4.5 Extracellular Network Formation 5.5 Collagen IV Receptors 5.5.1 Integrin Receptors 5.5.2 Non-integrin Receptors 5.6 Collagen IV Expression Patterns 5.7 Collagen IV Pathologies 5.7.1 COL4A1 Syndrome and Mutations in COL4A1 and COL4A2 5.7.1.1 Cerebrovascular and Cerebral Defects in COL4A1 Syndrome 5.7.1.2 PADMAL and Altered Collagen IV Levels 5.7.1.3 Ocular Disease 5.7.1.4 Neuromuscular Disease 5.7.1.5 HANAC and Kidney Defects 5.7.1.6 Additional Clinical Features in COL4A1 Syndrome 5.7.1.7 The Role of α1α1α2(IV) in Common Disease 5.7.2 Mutations and Diseases of α3α4α5(IV) and α5α5α6(IV) 5.7.2.1 Alport Syndrome 5.7.2.2 X-linked Alport Syndrome with Diffuse Leiomyomatosis 5.7.2.3 Goodpasture Syndrome 5.8 Disease Mechanisms 5.8.1 Developmental Origin to Adult Disease 5.8.2 Cellular Origins of Collagen IV Diseases 5.8.3 Molecular Disease Mechanisms 5.8.3.1 ECM Defects and Quantity and Quality of the Collagen Network 5.8.3.2 ER Stress as Disease Mechanism for Collagen IV Disorders 5.8.4 Environmental and Genetic Modifiers 5.9 Therapeutic Strategies 5.9.1 Gene Therapy and Therapies Targeting Downstream Mechanisms 5.9.2 Targeting ER Stress 5.10 Concluding Remarks References Chapter 6: Collagens and Muscle Diseases: A Focus on Collagen VI 6.1 Introduction 6.2 Collagen VI: Structure, Expression, and Binding Partners 6.2.1 Structure 6.2.2 Expression 6.2.3 Binding Partners 6.3 Collagen VI-Related Myopathies 6.3.1 UCMD Typical Clinical Features 6.3.2 BM Typical Clinical Features 6.3.3 Myosclerosis and Other Phenotypes 6.3.4 Mutations of COL6 Genes and Genotype-Phenotype Correlation 6.3.5 Diagnostic Tools 6.4 Animal Models for the Study of Collagen VI Pathophysiology 6.4.1 Col6a1 Knockout Mouse 6.4.1.1 Muscle Structural Defects 6.4.1.2 Alterations in Mitochondrial Function and Oxidative Stress Pathways 6.4.1.3 Dysregulated Autophagy 6.4.1.4 Further Processes Affected by ColVI Deficiency 6.4.1.5 ColVI in Muscle Stem Cell Homeostasis 6.4.1.6 ColVI in the Neuromuscular Junction 6.4.2 Col6a3 Mutant Mice 6.4.3 Zebrafish Models of ColVI-Related Diseases 6.5 Prospective Therapies and Pilot Clinical Trials for ColVI-Related Myopathies 6.5.1 RNA Targeting in COL6 Myopathies 6.5.2 Approaches Targeting Altered Molecular Pathways 6.5.2.1 Mitochondria 6.5.2.2 Oxidative Stress and Apoptosis 6.5.2.3 Autophagy 6.6 Other Collagens Involved in Myopathies and Inherited Muscle Disorders 6.6.1 Collagen IV 6.6.2 Collagen IX 6.6.3 Collagen XII 6.6.4 Collagen V 6.6.5 Collagen XV 6.6.6 Collagen XXII 6.6.7 Collagen XIII and Collagen Q 6.7 Conclusions References Chapter 7: Skin Blistering and Collagens: From Bench to Therapies 7.1 Introduction 7.2 The Players 7.2.1 Collagen VII 7.2.2 Collagen XVII 7.3 Skin Fragility 7.4 Dystrophic Epidermolysis Bullosa 7.5 Junctional Epidermolysis Bullosa 7.6 Autoimmune Blistering Disorders Associated with Autoantibodies Against Collagen XVII or Collagen VII 7.7 Evidence-Based and Regenerative Therapies 7.8 Outlook References Chapter 8: Collagens as New Players in Nervous System Diseases 8.1 Extracellular Matrix of the Nervous System 8.1.1 ECMs of the Central Nervous System 8.1.2 ECMs of the Peripheral Nervous System 8.2 Distribution of Collagen Subtypes in the Nervous System 8.2.1 Fibrillar Collagens and Other Fibril-Forming Collagens 8.2.2 FACIT Collagens 8.2.3 Network-Forming Collagens 8.2.4 Multiplexin Collagens 8.2.5 Transmembrane Collagens 8.3 Collagen Functions in the Nervous System 8.3.1 Neuronal Migration 8.3.2 Barrier and Filtration Functions 8.3.3 Neural Circuit Assembly, Maturation, and Maintenance 8.3.4 Myelination 8.3.5 Neurodevelopmental/Psychiatric/Degenerative Diseases 8.3.6 Reactive Collagen Production/Distribution Following Disease or Trauma 8.4 Conclusion References