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Dyneins
Structure, Biology and Disease
1st Edition - June 25, 2011
Editor: Stephen M. King
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 1 0 3 7 1 - 5
Hardback ISBN:
9 7 8 - 0 - 1 2 - 3 8 2 0 0 4 - 4
eBook ISBN:
9 7 8 - 0 - 1 2 - 3 8 2 0 0 5 - 1
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… Read more
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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.
- 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
Laboratory and clinical researchers across cell biology, developmental biology, genetics, protein chemistry, neurobiology, biophysics, biomedicine and medicine.
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
- No. of pages: 656
- Language: English
- Published: June 25, 2011
- Imprint: Academic Press
- Paperback ISBN: 9780128103715
- Hardback ISBN: 9780123820044
- eBook ISBN: 9780123820051
SK
Stephen M. 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