| | Contents | |
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| | Preface | XV |
| | List of Contributors | XVII |
| | Color Plates | XXIII |
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| Part I | Microtubule Organization and Dynamics | 1 |
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| 1 | Early Studies on Centrioles and Centrosomes Joseph G. Gall | 3 |
| 1.1 | Introduction | 3 |
| 1.2 | Pioneering Studies | 4 |
| 1.3 | Self-replication versus De Novo Formation | 7 |
| 1.4 | Centrioles and Basal Bodies | 7 |
| 1.5 | Blepharoplasts | 9 |
| 1.6 | The Search for DNA | 11 |
| 1.7 | On to Self-assembly | 12 |
| | References | 14 |
| 2 | The Tubulin Superfamily Tim Stearns | 17 |
| 2.1 | History | 17 |
| 2.2 | Family Relations | 18 |
| 2.3 | Localization and Function | 21 |
| 2.4 | -Tubulin | 21 |
| 2.5 | -Tubulin | 22 |
| 2.6 | -Tubulin | 22 |
| 2.7 | Other Members of the Fold | 23 |
| | References | 24 |
| 3 | Microtubule Nucleation Michelle Moritz, Luke M. Rice and David A. Agard | 27 |
| 3.1 | Introduction | 27 |
| 3.1.1 | The Nucleation of Microtubules can occur Spontaneously In Vitro, but Requires -Tubulin In Vivo | 28 |
| 3.1.2 | Models for the Mechanism of -TuRC/Tub4 Complex-mediated Microtubule Nucleation | 29 |
| 3.2 | Kinetic Models of the Mechanism of Microtubule Nucleation | 31 |
| 3.3 | The Involvement of Non- -TuRC Proteins in Microtubule Nucleation | 36 |
| 3.4 | Future Directions | 37 |
| | Acknowledgments | 38 |
| | References | 38 |
| 4 | The Budding Yeast Spindle Pole Body: A Centrosome Analog Suzanne van Kreeveld Naone and Mark Winey | 43 |
| 4.1 | Introduction | 43 |
| 4.2 | Molecular Composition of the Spindle Pole Body | 45 |
| 4.2.1 | The Central Plaque | 47 |
| 4.2.2 | The Inner Plaque | 48 |
| 4.2.3 | The Outer Plaque | 49 |
| 4.2.4 | Nuclear Membrane Factors | 49 |
| 4.2.5 | The Halfbridge | 50 |
| 4.2.6 | Structure Summary | 50 |
| 4.3 | Microtubule Nucleation | 51 |
| 4.4 | Assembly/Duplication of SPBs and Centrosomes | 53 |
| 4.4.1 | Electron Microscopic Description of Duplication | 53 |
| 4.4.2 | Cell Cycle Regulation of Duplication | 55 |
| 4.4.3 | Genetic Analysis of Duplication | 55 |
| 4.5 | Signaling Platform | 57 |
| 4.6 | Developmental Alteration of SPB Function | 60 |
| 4.7 | Parting Thoughts | 61 |
| | Acknowledgments | 61 |
| | References | 62 |
| 5 | Dissection of Basal Body and Centriole Function in the Unicellular Green Alga Chlamydomonas reinhardtii Susan K. Dutcher | 71 |
| 5.1 | Introduction | 71 |
| 5.2 | Why Study a Green Alga to Learn about Centrioles and Basal Bodies? | 72 |
| 5.3 | Structure of the Basal Body and Centriole in Chlamydomonas | 72 |
| 5.4 | Additional Fibers that Connect Basal Bodies and Centrioles | 76 |
| 5.4.1 | Contractile Fibers | 76 |
| 5.4.2 | Rootlet Microtubules | 77 |
| 5.4.3 | Non-contractile Fibers | 77 |
| 5.5 | Overview of the Cell Cycle of Chlamydomonas | 78 |
| 5.6 | Duplication of Basal Bodies in Chlamydomonas | 78 |
| 5.7 | Role of Tubulin Isoforms in Basal Body Duplication | 82 |
| 5.8 | Timing of Basal Body/Centriole Duplication in Chlamydomonas | 83 |
| 5.9 | Function of Basal Bodies and Centrioles in Chlamydomonas | 83 |
| 5.10 | What Makes a Basal Body Different from a Centriole? | 84 |
| 5.10.1 | Transition Zone and Docking | 84 |
| 5.10.2 | Transition Zone and Autonomy | 84 |
| 5.10.3 | Maturation of Basal Bodies | 86 |
| 5.11 | Conclusion | 87 |
| | Acknowledgments | 87 |
| | References | 88 |
| 6 | The Centrosome in Evolution Juliette Azimzadeh and Michel Bornens | 93 |
| 6.1 | Introduction | 93 |
| 6.2 | The Centriole/Basal Body Structure is a Derived Characteristic of Eukaryotes | 94 |
| 6.3 | The Basal Body/Axoneme is the Ancestral Structure | 94 |
| 6.4 | Functions Associated with the Flagellar Apparatus | 96 |
| 6.4.1 | Cell Locomotion | 97 |
| 6.4.2 | Sensory Reception | 97 |
| 6.4.3 | Cell Division | 98 |
| 6.5 | The Conservative Mode of Duplication of the Basal Body/Centriole/SPB: An Essential Clue for Cell Morphogenesis | 100 |
| 6.6 | The Centrosome or Central Body | 102 |
| 6.7 | Evolution of Centrosome-associated Gene Products | 104 |
| 6.7.1 | -Tubulin | 104 |
| 6.7.2 | Centrin | 106 |
| 6.7.3 | Centrin-binding Proteins | 111 |
| 6.8 | Conclusion: The Centrosome -- A Cell Individuation Organ? | 113 |
| 6.8.1 | Survival Value of Coupling Basic Functional Modules on the Same Organ | 113 |
| 6.8.2 | Co-Evolution of the Centrosome and the Cleavage Apparatus | 114 |
| 6.8.3 | The Biological Significance of Having a Cell Center | 115 |
| | Acknowledgments | 116 |
| | References | 116 |
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| Part II | The Integration of Centrosome and Chromosome Cycles | 123 |
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| 7 | A Proteomic Approach to the Inventory of the Human Centrosome Christopher J. Wilkinson, Jens S. Andersen, Matthias Mann and Erich A. Nigg | 125 |
| 7.1 | Introduction | 125 |
| 7.2 | What is a Centrosome Component? | 126 |
| 7.3 | Composition of the Human Centrosome: A Proteomic Approach | 127 |
| 7.4 | Inspection of Novel Centrosome Proteins by Sequence Analysis | 132 |
| 7.5 | Cell Cycle Changes in Centrosome Composition | 135 |
| 7.6 | The Impact of MS on Centrosome Analysis during Cell Cycle and Development | 137 |
| 7.7 | Expanding Proteomic Information into Knowledge about Function | 138 |
| 7.8 | Conclusion and Prospects | 138 |
| | Acknowledgments | 139 |
| | References | 139 |
| 8 | The Role of the Centrosome in Cell Cycle Progression Andrew M. Fry and Rebecca S. Hames | 143 |
| 8.1 | Introduction | 143 |
| 8.2 | Cell Cycle Dynamics of Centrosome Structure | 144 |
| 8.3 | Old and New Functions of the Centrosome | 145 |
| 8.4 | The Centrosome in G2/M Control | 146 |
| 8.5 | Initiation of Cyclin B Destruction at the Centrosome | 149 |
| 8.6 | The Contribution of Centrosomes to Cytokinesis | 153 |
| 8.7 | A Role for Centrosomes in G1/S Progression? | 157 |
| 8.8 | In Conclusion | 159 |
| | Acknowledgments | 159 |
| | References | 160 |
| 9 | Centrosome Duplication and its Regulation in the Higher Animal Cell Greenfield Sluder | 167 |
| 9.1 | Introduction | 167 |
| 9.2 | The Events of Centrosome Reproduction | 168 |
| 9.2.1 | Centriole Disorientation | 168 |
| 9.2.2 | Centriole Duplication | 169 |
| 9.2.3 | Centrosome Disjunction | 170 |
| 9.2.4 | Centrosome Separation | 170 |
| 9.2.5 | Some Proteins Needed for Centrosome Reproduction | 172 |
| 9.3 | Control of Centrosome Duplication | 173 |
| 9.3.1 | Control of Centrosome Number: Intrinsic Mechanisms | 173 |
| 9.3.2 | Block to Re-replication | 175 |
| 9.3.3 | Time of Centrosome Duplication: Extrinsic Controls | 176 |
| 9.3.4 | Cyclin-dependent Kinases in the Control of Centrosome Reproduction | 176 |
| 9.3.4.1 | Zygote Systems | 177 |
| 9.3.4.2 | Mammalian Somatic Cells | 177 |
| 9.3.5 | Targets of Cdk2--Cyclin E Kinase | 179 |
| 9.3.6 | Other Kinases Involved in Centrosome Duplication | 180 |
| 9.3.7 | Ubiquitin-mediated Proteolysis in the Control of Centrosome Duplication | 181 |
| 9.4 | Closing Remarks | 183 |
| | Acknowledgments | 183 |
| | References | 183 |
| 10 | A Synergy of Technologies: Using Green Fluorescent Protein Tagging and Laser Microsurgery to Study Centrosome Function and Duplication in Vertebrates Alexey Khodjakov and Conly L. Rieder | 191 |
| 10.1 | Introduction | 191 |
| 10.2 | Laser Microsurgery | 193 |
| 10.2.1 | A Brief History of Development | 193 |
| 10.2.2 | Utility for Removing the Centrosome | 195 |
| 10.3 | Roles of the Centrosome during Cell Division | 199 |
| 10.3.1 | Role of the Centrosome during Spindle Assembly | 199 |
| 10.3.2 | Role of the Centrosome during Cytokinesis | 202 |
| 10.4 | The Centrosome in the Cell Cycle | 203 |
| 10.4.1 | Role of the Centrosome in Progression through the Cell Cycle | 203 |
| 10.4.2 | De Novo Centrosome Formation | 205 |
| 10.5 | For the Future | 208 |
| | Acknowledgments | 208 |
| | References | 209 |
| 11 | Centrosome Regulation in Response to Environmental and Genotoxic Stress Ody C. M. Sibon and William E. Theurkauf | 211 |
| 11.1 | Introduction | 211 |
| 11.2 | Heat Shock | 211 |
| 11.3 | Centrosomes and the Unfolded Protein Response | 213 |
| 11.4 | Centrosome Disruption in Response to Genotoxic Stress | 215 |
| 11.4.1 | Centrosome Inactivation in Early Embryos | 215 |
| 11.4.2 | Chk2 is Required for DNA Damage-induced Mitotic Catastrophe | 216 |
| 11.4.3 | DNA Damage and Mitosis in Mammalian Cells | 218 |
| 11.5 | Final Thoughts | 219 |
| | References | 221 |
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| Part III | The Centrosome in Development and Tissue Architecture | 225 |
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| 12 | The C. elegans Centrosome during Early Embryonic Development Laurence Pelletier, Thomas Müller-Reichert, Martin Srayko, Nurhan Özlü, Anne-Lore Schlaitz and Anthony A. Hyman | 227 |
| | Abbreviations | 227 |
| 12.1 | Introduction | 227 |
| 12.1.1 | C. elegans as a Tool to Study Centrosome Biogenesis | 227 |
| 12.1.2 | The First Cell Division of the C. elegans Embryo | 228 |
| 12.2 | The C. elegans Centrosome | 230 |
| 12.2.1 | The Centrioles | 231 |
| 12.2.2 | The Pericentriolar Material (PCM) | 233 |
| 12.3 | The Centrosome Cycle in C. elegans Embryos | 234 |
| 12.3.1 | Centriole Duplication | 236 |
| 12.3.2 | PCM Recruitment | 237 |
| 12.3.3 | Centrosome Maturation | 238 |
| 12.4 | Centrosome Functions | 240 |
| 12.4.1 | Spindle Assembly and Microtubule Nucleation | 240 |
| 12.4.2 | Determination of Anterior--Posterior Polarity | 242 |
| 12.4.3 | Spindle Positioning | 243 |
| 12.5 | Concluding Remarks | 244 |
| | Acknowledgments | 245 |
| | References | 245 |
| 13 | Centrosomes in a Developing Organism: Lessons from Drosophila Jordan W. Raff | 251 |
| 13.1 | Introduction | 251 |
| 13.2 | Centrosome and Microtubule Organisation during the Drosophila Life Cycle | 251 |
| 13.2.1 | Oogenesis | 251 |
| 13.2.2 | Spermatogenesis | 253 |
| 13.2.3 | Early Embryogenesis | 254 |
| 13.2.4 | Asymmetric Divisions of Embryonic Neuroblasts | 255 |
| 13.2.5 | Larval Development | 256 |
| 13.3 | Drosophila Centrosomal Proteins | 257 |
| 13.3.1 | Microtubule Nucleation from Centrosomes: -Tubulin and the -TuRC | 257 |
| 13.3.2 | The Recruitment of the -TuRC to Centrosomes: The Potential Roles of Asp, Polo, CNN, Aurora A, and CP309/D-PLP | 258 |
| 13.3.3 | The Interaction between Centrosomes and Microtubules: The Role of D-TACC and Msps | 259 |
| 13.3.4 | Centrosomes and the Organization of the Actin/Myosin Cytoskeleton in Early Fly Embryos: The Role of Scrambled, Nuf, and CP190 | 260 |
| 13.3.5 | Centrosomes and Cytokinesis: Studies on asl, cnn, and -Tubulin Mutant Spermatocytes | 262 |
| 13.3.6 | Centrosomes and the Cell Cycle | 263 |
| 13.3.7 | Centrosome Dynamics: Inactivation and Flares | 264 |
| 13.3.8 | Microtubule Motors and Plus-end Tracking Proteins at the Centrosome | 265 |
| 13.3.9 | The Interphase Centrosome in Flies: Missing in Action? | 265 |
| 13.4 | The Role of Centrosomes and Centrosomal Proteins In Vivo | 266 |
| 13.4.1 | The Essential Role of Centrosomes In Drosophila | 266 |
| 13.4.2 | The Role of Centrosomal Proteins in Oogenesis | 268 |
| 13.5 | Summary | 270 |
| | Acknowledgments | 270 |
| | References | 270 |
| 14 | Centrosome Inheritance during Human Fertilization and “Therapeutic” Cloning: Reproductive and Developmental Diseases and Disorders Caused by Centrosome Dysfunction C. S. Navara, C. Simerly and G. Schatten | 279 |
| 14.1 | Introduction | 279 |
| 14.2 | Centrosomes during Human Fertilization | 281 |
| 14.3 | Centrosome Dysfunction as Causes of Human Infertility | 281 |
| 14.4 | Centrosome Functional Assays for Diagnosing Male Infertility | 284 |
| 14.5 | Polyspermy in Humans | 285 |
| 14.6 | „Dispermy Hypothesis“ for the Origins of Genomic Imprinted Disorders | 287 |
| 14.7 | Maternal Centrosome Anomalies and Birth Defects | 288 |
| 14.8 | Resolving the Special Problem of Parthenogenesis: Roles of Cytoplasmic Motors and NuMA | 289 |
| 14.9 | Centrosomes during Cloning, and Centrosomes in Embryonic Stem Cells Derived after Nuclear Transfer | 290 |
| 14.10 | Research Challenges for Centrosome Developmental Biologists: Developmental Centrosomopathies | 292 |
| | References | 293 |
| 15 | Microtubule Organizing Centers in Polarized Epithelial Cells Mette M. Mogensen | 299 |
| 15.1 | Introduction | 299 |
| 15.2 | Centrosomal Microtubule Nucleation | 300 |
| 15.3 | Non-centrosomal Microtubule Arrays | 301 |
| 15.4 | Microtubule Minus-end Anchorage at Centrosomal and Non-centrosomal Sites | 305 |
| 15.5 | Centrosomal Release of Microtubules and Anchoring Complexes | 307 |
| 15.6 | Stabilization of Non-centrosomal Microtubules | 308 |
| 15.7 | Release and Capture | 310 |
| | Acknowledgments | 312 |
| | References | 312 |
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| Part IV | Centrosomes in Disease | 321 |
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| 16 | Centrosome Anomalies in Cancer: From Early Observations to Animal Models Thea M. Goepfert and William R. Brinkley | 323 |
| 16.1 | Early Observations | 323 |
| 16.2 | Origin of Centrosome Anomalies | 326 |
| 16.2.1 | Deregulation of Centrosome Duplication | 326 |
| 16.2.2 | De Novo Formation of Centrioles or Uncontrolled Separation of Centriole Pairs | 327 |
| 16.2.3 | Failure to Undergo Cytokinesis | 327 |
| 16.2.4 | Fusion of Cells | 327 |
| 16.3 | Animal Models | 328 |
| 16.3.1 | Centrosome Anomalies and the p53 Pathway | 328 |
| 16.3.2 | Centrosome Anomalies and BRCA 1 | 329 |
| 16.3.3 | Centrosome Anomalies and Aurora A | 330 |
| | Acknowledgments | 333 |
| | References | 333 |
| 17 | Radiation Therapy and Centrosome Anomalies in Pancreatic Cancer Norihiro Sato, Kazuhiro Mizumoto, and Masao Tanaka | 337 |
| | Abstract | 337 |
| 17.1 | Introduction | 337 |
| 17.2 | Radiation-induced Cell Death: Apoptosis or Mitotic Cell Death? | 338 |
| 17.3 | Centrosome Anomalies Induced by Radiation | 339 |
| 17.4 | The Mechanism(s) Leading to Centrosome Anomalies after Radiation Treatment | 341 |
| 17.5 | The Consequence of Centrosome Anomalies after Irradiation | 343 |
| 17.6 | Factors Affecting Centrosome Anomalies after Irradiation | 345 |
| 17.7 | Conclusions and Future Directions | 346 |
| | References | 347 |
| 18 | Human Papillomavirus Infection and Centrosome Anomalies in Cervical Cancer Karl Münger and Stefan Duensing | 353 |
| 18.1 | Genomic Instability and Malignant Progression | 353 |
| 18.2 | Human Papilloma viruses | 354 |
| 18.3 | Biological Activities of HPV E6/E7 Oncogenes | 355 |
| 18.4 | HPV-mediated Cervical Carcinogenesis as a Model System to Study Genomic Instability and Malignant Progression | 357 |
| 18.5 | Centrosome Abnormalities and Genomic Instability: Cause or Effect? | 358 |
| 18.6 | Induction of Centrosome Abnormalities by HPV Oncoproteins: Boveri’s Model Revisited | 359 |
| 18.7 | Do HPV E7-induced Centrosome Anomalies Contribute to Carcinogenic Progression? | 362 |
| 18.8 | Mechanistic Considerations | 363 |
| 18.9 | Concluding Remarks | 365 |
| | Acknowledgments | 366 |
| | References | 367 |
| 19 | Manipulation of Centrosomes and the Microtubule Cytoskeleton during Infection by Intracellular Pathogens Niki Scaplehorn and Michael Way | 371 |
| 19.1 | Introduction | 371 |
| 19.2 | Microtubule-directed Movement of Viruses and Membrane Compartments during Viral Infection | 372 |
| 19.2.1 | Targeting the Nucleus using Motor-proteins and the Microtubule Network: Herpes Simplex Virus, Poliovirus and Retroviruses | 373 |
| 19.2.2 | Hijacking Motor Proteins to Promote Cytoplasmic Assembly and Spread: Vaccinia Virus and African Swine Fever Virus | 375 |
| 19.2.3 | Conclusion | 379 |
| 19.3 | Virus-mediated Damage to the Centrosome and Microtubule Network | 380 |
| 19.3.1 | Viral Disruption of Microtubule Organization | 380 |
| 19.3.2 | Virus-mediated Centrosomal Damage | 381 |
| 19.3.3 | Summary | 383 |
| 19.4 | Viral Disruption of the Centrosome Duplication Cycle and Spindle Checkpoints | 383 |
| 19.4.1 | Early Studies on Centrosome Number: Paramyxoviral Syncytia | 384 |
| 19.4.2 | Multiple Centrosomes: Human Immunodeficiency Virus and the DNA Damage Checkpoint | 385 |
| 19.4.3 | Multiple Centrosomes: DNA Tumor Viruses, Retinoblastoma and Ran GTPase | 387 |
| 19.4.4 | Targeting the Spindle Assembly Checkpoint: Human T-Cell Leukemia Virus-1 | 388 |
| 19.4.5 | Summary | 389 |
| 19.5 | Bacterial Manipulation of the Centrosome and Microtubules | 390 |
| 19.5.1 | Bacterial Manipulation of the Microtubule Network | 390 |
| 19.5.2 | Interactions between Bacteria and the Centrosome | 393 |
| 19.5.3 | Summary | 394 |
| 19.6 | Conclusion | 394 |
| | Acknowledgments | 394 |
| | References | 395 |
| 20 | Basal Bodies and Microtubule Organization in Pathogenic Protozoa Keith Gull, Laura Briggs and Sue Vaughan | 401 |
| 20.1 | Introduction and Appreciation | 401 |
| 20.2 | The „Dispersed“ MTOC Complement of Protozoal Cells | 403 |
| 20.3 | The Trypanosoma brucei Microtubule Biology | 403 |
| 20.3.1 | The Spindle and Cell Division | 404 |
| 20.3.2 | Basal Bodies | 407 |
| 20.4 | The Microtubule Biology of the Apicomplexa | 408 |
| 20.4.1 | The Apical Polar Ring: A Unique Cytoplasmic MTOC | 408 |
| 20.4.2 | The Conoid | 409 |
| 20.4.3 | Apicomplexan Basal Bodies | 410 |
| 20.4.4 | The Spindle MTOC | 411 |
| 20.4.5 | Apicomplexan Cell Division and Cell Morphogenesis | 411 |
| 20.5 | Basal Bodies Are More than Just Microtubule Organizers: The Hitchhiker’s Guide to the Cytoskeleton! | 414 |
| 20.6 | Cytoskeletal Adaptations to Parasitism | 416 |
| 20.7 | Conclusion | 419 |
| | Acknowledgments | 420 |
| | References | 420 |
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