Dyneins

Dyneins

Structure, Biology and Disease

1st Edition - June 25, 2011
  • Editor: Stephen King
  • Paperback ISBN: 9780128103715
  • eBook ISBN: 9780123820051

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Description

Research on dyneins has a direct impact on human diseases, such as viruses and cancer. With an accompanying website showing over 100 streaming videos of cell dynamic behavior for best comprehension of material, Dynein: Structure, Biology and Disease is the only reference covering the structure, biology and application of dynein research to human disease. From bench to bedside, Dynein: Structure, Biology and Disease offers research on fundamental cellular processes to researchers and clinicians across developmental biology, cell biology, molecular biology, biophysics, biomedicine, genetics and medicine.

Key Features

  • Broad-based up-to-date resource for the dynein class of molecular motors
  • Chapters written by world experts in their topics
  • Numerous well-illustrated figures and tables included to complement the text, imparting comprehensive information on dynein composition, interactions, and other fundamental features

Readership

Laboratory and clinical researchers across cell biology, developmental biology, genetics, protein chemistry, neurobiology, biophysics, biomedicine and medicine.

Table of Contents

  • List of Contributors

    Preface

    1. Discovery of Dynein and its Properties

    1.1. Introduction

    1.2. Research at Harvard

    1.3. Research at the University of Hawaii

    1.4. Semi-Retirement in Berkeley

    1.5. The Pluses of Working on a Minus-End-Directed Motor

    1.6. Epilogue

    2. Evolutionary Biology of Dyneins

    2.1. Introduction

    2.2. Dynein Classification

    2.3. Dynein Evolution in Eukaryotes

    2.4. Evolution in the Proto-Eukaryote

    2.5. The Origins of Dynein

    2.6. Summary

    3. The AAA+ Powerhouse – Trying to Understand How it Works

    3.1. Introduction

    3.2. Sequence analysis of the Dynein AAA+ Domains

    3.3. Nucleotide Binding in the Motor Domain

    3.4. How are the AAA+ Modules Spatially Arranged?

    3.5. Communication of the Motor Domain with the Microtubule-Binding Domain

    3.6. Transduction of Local Conformational Changes into Motion

    3.7. Conclusion

    4. Dynein Motor Mechanisms

    4.1. The Dynein Engine Room

    4.2. The Linker Arm and Powerstroke

    4.3. Microtubule Affinity: Binding at A Distance

    4.4. A Three-Part Harmony in A Big Block V-8

    5. Structural Analysis of Dynein Intermediate and Light Chains

    5.1. Introduction

    5.2. Abbreviated Background of Light Chains

    5.3. Structure of The Apo Light Chains

    5.4. Structure of Liganded Light Chains

    5.5. LC8 and Tctex1 Promiscuity

    5.6. Light Chain Isoforms

    5.7. Mammalian Dynein Intermediate Chains

    5.8. Molecular Model of the Light Chain–Intermediate Chain Structure

    5.9. Light Chains and Cargo

    5.10. Post-Translational Modifications

    5.11. The Roles of LC8 and Tctex1 on Dynein

    5.12. Summary

    6. Biophysics of Dynein In Vivo

    6.1. Single-Molecule Properties of Dynein In Vitro

    6.2. Multiple-Motor Properties of Dynein In Vitro

    6.3. Regulation of Dynein In Vitro

    6.4. Regulation of Dynein In Vivo

    6.5. Single-Molecule Properties of Dynein In Vivo

    6.6. Regulation of Unidirectional Dynein-Based Transport: Vesicular Cargos

    6.7. Regulation of Unidirectional Dynein-Based Transport: Large Cargos

    6.8. Regulation of Bidirectional Dynein-Based Transport

    7. Composition and Assembly of Axonemal Dyneins

    7.1. Introduction

    7.2. Classes of Dynein Components

    7.3. Monomeric Inner Dynein Arms

    7.4. Dimeric Inner Dynein Arm I1/f

    7.5. Outer Dynein Arms

    7.6. Inter-Dynein Linkers

    7.7. Properties and Organization of Axonemal Dynein Motor Units

    7.8. Core WD-Repeat Intermediate Chains Associated with Oligomeric Motors

    7.9. Additional Intermediate Chains

    7.10. Core Light Chains Associated with Oligomeric Motors

    7.11. Regulatory Components

    7.12. Docking Motors onto the Axoneme

    7.13. Other Dynein-Associated Components

    7.14. Pathways of Axonemal Dynein Assembly and Transport

    7.15. Conclusions

    8. Organization of Dyneins in the Axoneme

    8.1. Introduction

    8.2. The History of Methodological Development in Structural Research into Axonemal Dynein

    8.3. Dynein Arm Arrangement In Situ

    8.4. Inner Dynein Arm Structure In Situ

    8.5. Outer Dynein Arm Structure In Situ

    8.6. Heterogeneity and Asymmetry of Structure and Arrangement of Dynein in the Axoneme

    8.7. Thoughts on Dynein Functions Based on In Situ Structure

    8.8. Outlook

    9. Genetic Approaches to Axonemal Dynein Function in Chlamydomonas and Other Organisms

    9.1. Introduction

    9.2. Genetic Studies of Chlamydomonas Axonemal Dyneins

    9.3. Genetic Studies in Various Organisms

    9.4. Conclusion and Perspective

    10. Regulation of Axonemal Outer-Arm Dyneins in Cilia

    10.1. Introduction: Structure, Subunit Composition, and Arrangement of Outer-Arm Dynein

    10.2. Fundamental Sliding Activity of Outer-Arm Dynein

    10.3. Intra-Outer-Arm Dynein (Inter-Heavy Chain) Regulations

    10.4. Inter-Outer-Arm Dynein Regulation

    10.5. Regulation of Outer-Arm Dynein Activity by External Signals

    10.6. Conclusion

    11. Control of Axonemal Inner Dynein Arms

    11.1. Overview

    11.2. Organization of the Inner Dynein Arms in the Axoneme

    11.3. Regulation of I1 Dynein by Second Messengers and Phosphorylation

    11.4. Current Questions

    12. Flagellar Motility and the Dynein Regulatory Complex

    12.1. Introduction

    12.2. The Central Pair, Radial Spokes, and Dynein Regulatory Complex

    12.3. The Dynein Heavy Chain Suppressors

    12.4. The Dynein Regulatory Complex and the Inner Dynein Arms

    12.5. The Dynein Regulatory Complex and Nexin Link

    12.6. Localization of Dynein Regulatory Complex Subunits Within the Nexin Link

    12.7. Identification and Characterization of Dynein Regulatory Complex and Nexin Subunits

    12.8. Function of the Dynein Regulatory Complex–Nexin Link in Motility and Future Directions

    13. Regulation of Dynein in Ciliary and Flagellar Movement

    13.1. Introduction

    13.2. Basic Features of the Components of Cilia and Flagella

    13.3. Regulation of Microtubule Sliding in the Axoneme

    13.4. Sliding Microtubule Theory and Bend Formation

    13.5. The Mechanism of Oscillation

    13.6. Outlook

    14. Dynein and Intraflagellar Transport

    14.1. Introduction

    14.2. Intraflagellar Transport

    14.3. Discovery of the Cytoplasmic Dynein 2 Heavy Chain and Early Proposals for its Function

    14.4. Identification of Cytoplasmic Dynein 2 as The Intraflagellar Transport Retrograde Motor

    14.5. Structure and Subunit Content of Cytoplasmic Dynein 2

    14.6. Function of Cytoplasmic Dynein 2 and Retrograde Intraflagellar Transport

    14.7. Conclusion

    15. Cytoplasmic Dynein Function Defined by Subunit Composition

    15.1. Introduction

    15.2. Heavy Chain (DYNC1H)

    15.3. Light Intermediate Chain (DYNC1LI)

    15.4. Intermediate Chain (DYNC1I)

    15.5. Dynll (LC8 Light Chain)

    15.6. DYNLT (Tctex1 Light Chain)

    15.7. DYNLRB (Roadblock Light Chain)

    15.8. Conclusion

    16. Studies of Lissencephaly and Neurodegenerative Disease Reveal Novel Aspects of Cytoplasmic Dynein Regulation

    16.1. Introduction

    16.2. Extramolecular Regulation of Cytoplasmic Dynein Force Generation by LIS1 and NudE/NudEL

    16.3. Intramolecular Regulation of Dynein Processivity and Implications for Neurodegeneration

    16.4. Conclusion

    17. Insights into Cytoplasmic Dynein Function and Regulation from Fungal Genetics

    17.1. Introduction

    17.2. Discoveries of Dynein Function in Spindle Orientation/Nuclear Migration

    17.3. Identification of Dynein Regulators Using Fungal Genetics

    17.4. Dissecting the Mechanism and Function of the Microtubule-Plus-End Accumulation of Cytoplasmic Dynein

    17.5. Understanding The Functions of Various Components of the Dynein and Dynactin Complexes

    17.6. Conclusions

    18. Genetic Insights into Mammalian Cytoplasmic Dynein Function Provided by Novel Mutations in the Mouse

    18.1. Why, and How, We Work with Mice to Learn About Mammalian Genes such as the Dynein Subunits

    18.2. Approaches to Working with Mouse Mutants to Learn About Dynein Function

    18.3. Accessing Information About Mouse Mutants

    18.4. Genetic Background is Important

    18.5. Mouse Strains with Mutations in Cytoplasmic Dynein Subunits

    18.6. A Further Note on Nomenclature

    18.7. An Allelic Series of Mutations in the Mouse Cytoplasmic Dynein Heavy Chain Gene, Dync1h1

    18.8. Overall Conclusions from the Dync1h1 Mutant Mice

    18.9. The MMTV-DLCS88A Transgenic Mouse

    18.10. Using Mouse Genetics to Further Unravel the Role of the Cytoplasmic Dynein Heavy Chain

    18.11. Conclusion

    19. The Role of Dynactin in Dynein-Mediated Motility

    19.1. Introduction

    19.2. Structure and Composition of Dynactin

    19.3. Known Activities of Dynactin

    19.4. Dynactin Function in Dynein-Based Motility

    20. Roles of Cytoplasmic Dynein During Mitosis

    20.1. Introduction

    20.2. Model Systems of Mitotic Dynein

    20.3. Spindle Pole Dynein

    20.4. Cortical Dynein

    20.5. Kinetochore Dynein

    20.6. Phosphorylation

    20.7. Future Questions

    20.8. Conclusions

    21. Does Dynein Influence the Non-Mendelian Inheritance of Chromosome 17 Homologs in Male Mice?

    21.1. Introduction

    21.2. Properties of Tctex1

    21.3. Properties of Tctex2

    21.4. Properties of Dnahc8

    21.5. Chromosomal Deletion Analysis Modifies Lyon’s Model

    21.6. Identification of Tcds

    21.7. What About Dyneins?

    22. Role of Dynein in Viral Pathogenesis

    22.1. General Tenets of Virus–Host Interactions

    22.2. Blocking Dynein Function in Virus-Infected Cells: Potential Drug Development to Poison Viral Replication Steps

    22.3. Direct Interactions with Dynein for Viral Entry: Trafficking Towards the Nucleus by Various Viruses

    22.4. Innate Immune Response to Viral Infection

    22.5. Dyneins and Stress Granule Assembly: A Novel Concept in Innate Responses to Viral Infection

    22.6. Dynein Involvement in Viral Egress and Assembly

    22.7. Using Dynein To Traffic to Virus Assembly Domains

    22.8. Cell-to-Cell Transmission

    22.9. Virus Export from Virus Factories

    22.10. Concluding Remarks

    23. Cytoplasmic Dynein Dysfunction and Neurodegenerative Disease

    23.1. Introduction

    23.2. Cytoplasmic Dynein Drives Intracellular Transport in Neurons

    23.3. Dynein Function in Developing Neurons

    23.4. Dynein Dysfunction in Neurodegeneration

    23.5. Dynein Mutations in Model Organisms

    23.6. Dynein's Role in the Pathogenesis of Common Neurodegenerative Disease

    23.7. Conclusions

    24. Dynein Dysfunction as a Cause of Primary Ciliary Dyskinesia and Other Ciliopathies

    24.1. Introduction

    24.2. Ultrastructure of Motile Cilia

    24.3. Outer Dynein Arms

    24.4. Inner Dynein Arms

    24.5. Ciliopathies

    24.6. Primary Cilia Dyskinesia

    24.7. Molecular Defects Affecting Outer Dynein Arm Components

    24.8. Molecular Defects Affecting Outer and Inner Dynein Arms

    24.9. Molecular Defects Affecting the Central Pair and Radial Spokes

    24.10. Molecular Defects Affecting Dynein Regulatory Complexes and Inner Dynein Arms

    Index

Product details

  • No. of pages: 656
  • Language: English
  • Copyright: © Academic Press 2011
  • Published: June 25, 2011
  • Imprint: Academic Press
  • Paperback ISBN: 9780128103715
  • eBook ISBN: 9780123820051

About the Editor

Stephen King

Stephen M. King is Professor of Molecular Biology and Biophysics at the University of Connecticut School of Medicine and is also director of the electron microscopy facility. He has studied the structure, function and regulation of dyneins for over 30 years using a broad array of methodologies including classical/molecular genetics, protein biochemistry, NMR structural biology and molecular modeling, combined with cell biological approaches, imaging and physiological measurements.

Affiliations and Expertise

Professor, Department of Molecular Biology and Biophysics Director, Electron Microscopy Facility, University of Connecticut Health Center