Aspects of the Cytoskeleton (eBook)

Cover 1
Copyright page 5
Table of contents 6
Contributors 10
Preface 12
Chapter 1: The Cytoskeleton of the Platelet 15
I. Introduction 16
II. Cytoskeleton of the Resting Platelet 16
A. Actin Cytoskeleton 16
B. Platelet Microtubule Coil 20
III. Rearrangement of the Cytoskeleton During Platelet Activation 21
A. Formation of Filopodia 22
B. Signaling Pathways Regulating the Cytoskeleton of the Platelet 23
IV. Rearrangement of the Cytoskeleton During Platelet Adhesion 28
A. Formation of Lamellipodia 28
V. Contractile Elements of the Platelet Cytoskeleton 29
VI. Inhibition of the Platelet Cytoskeleton by Cyclic Nucleotides 29
VII. Summary 32
References 32
Chapter 2: The Actin Cytoskeleton in the Apical Domain of Epithelial Cells 39
I. Introduction 40
II. Properties of Actin and Actin-Associated Proteins 40
A. Cellular Cytoskeleton 40
B. Individual Epithelial Cells Can Coexpress beta- and gamma-Actin Genes 41
C. Actin-Associated Proteins Harness the Potential of Actin Filaments 42
D. Arp2/3 Complex Nucleates Actin Filaments 42
E. Disassembly of Filaments Is an Essential Part of Actin Dynamics 43
F. Filaments Can be Stabilized from Dynamic Turnover 44
G. Stabilized Filaments Are Cross-Linked into Structural Lattices 44
H. Actin Filaments Are Tethered to the Plasma Membrane 45
I. Actin Cytoskeleton Is Used to Generate Force and Movement 46
III. Structural Organization of Actin Within Epithelial Cells 46
IV. Functional Contributions of the Actin Cytoskeleton in the Apical Domain 48
A. Trafficking of Exocytic Vesicles to the Apical Membrane 48
B. Moderating Access to the Plasma Membrane 50
C. Retaining Specific Proteins in the Apical Membrane 50
D. Moderating Activities of Proteins While in the Membrane 53
E. Recovering Proteins from the Membrane 53
V. Contribution of the Actin Cytoskeleton in Epithelial Disease States 54
A. Infectious Pathogens Hijack the Host Actin Cytoskeleton 54
B. Apical Membrane Structure Is Specifically Altered in Epithelial Diseases 55
C. Ischemia Results in Profound Structural and Functional Alterations 55
VI. Concluding Remarks 57
References 58
Chapter 3: The Connection Between Actin ATPase and Polymerization 63
I. Actin Microfilament System 63
II. Atomic Structure of the Actin Monomer 64
III. Profilin:beta-Actin Crystal 65
IV. Interdomain Connectivity in Actin 67
V. Actin ATPASE 68
A. Monomeric Actin Hydrolyzes ATP 68
B. Polymer Formation and ATP Hydrolysis 69
C. The Actin-ATP/ADPsdotPi Cap 69
VI. Mechanism of ATP Hydrolysis on Actin 70
A. Active Site Nucleophile 70
B. Catalytic Base(s) 71
VII. Actin Methylhistidine 73, ATPase, Phosphate Release, and Polymerization 72
VIII. Importance of the Status of the Actin-Bound Nucleotide 75
References 75
Chapter 4: Spectrin Function: A Survey of Genetic Systems from Drosophila to Humans 81
I. Introduction 82
II. Spectrin in the Red Blood Cell 82
III. The Spectrin Paradigm in Nonerythroid Cells 85
IV. Genetic Studies of Spectrin Cytoskeleton Function in Nonerythroid Cells 86
A. Human Genetic Studies 86
B. Genetic Studies of Spectrin and Ankyrin in the Mouse 86
V. Studies of the Spectrin Cytoskeleton in Drosophila 87
A. Characterization of the Protein Spectrin in Drosophila 87
B. Drosophila Ankyrins 88
C. Genetic Studies of Drosophila Spectrin 88
D. Evaluation of the Genetic Model 91
VI. Spectrin Assembly and Cell Polarity in Tissue Culture Models 92
A. Cell Adhesion as a Cue for Spectrin Assembly 92
B. Programed Formation of Specialized Regions of the Plasma Membrane 94
C. Ankyrin-Dependent Formation of a Membrane Domain 95
VII. Role of the PH Domain in Spectrin Assembly 96
VIII. Future Prospects 97
Acknowledgments 98
References 98
Chapter 5: Structure and Function of Villin 103
I. Introduction 103
II. Actin-Modifying Functions of Villin 106
III. Ligand-Binding Properties of Villin 114
IV. Posttranslational Modification of Villin 119
V. Villin's Role in Cell Migration 122
VI. Studies with Point Mutants 123
VII. Epithelial-to-Mesenchymal Transition 123
VIII. Villin as a Marker in Oncology 124
IX. Other Functions of Villin 125
Acknowledgments 126
References 127
Chapter 6: Roles of the Actin Cytoskeleton and Myosins in the Endomembrane System 133
I. Introduction 134
II. Actin Cytoskeleton in Movements Along the Biosynthetic Pathway 134
A. Golgi Actin Cytoskeleton 135
B. Actin Inhibition Affects Movements to and from Golgi 136
C. Role of Cdc42 in Recruiting Actin to the Golgi 136
D. Actin Polymerization Driven Transport in the Endomembrane System 138
III. Roles of Myosins in Membrane Movements Along Endomembrane Pathways 139
A. Myo1 139
B. Nonmuscle Myo2 140
C. Myo5 141
D. Myo6 142
IV. Conclusions 143
Acknowledgments 143
References 143
Chapter 7: The BRG1 and the Actin Filament System 149
I. Chromatin Remodeling 150
II. Effect of Chromatin Remodeling on the Actin Filament System 151
A. SWI/SNF Chromatin-Remodeling Complexes Are Involved in the Actin Filament Organization 152
III. Actin in the Nucleus 157
A. Actin in Nuclear Processes 157
B. Actin and ARPs in Chromatin-Remodeling Complexes 160
References 167
Chapter 8: Ionic Waves Propagation Along the Dendritic Cytoskeleton as a Signaling Mechanism 177
I. Introduction 178
II. The Interrelation Between the Neural Cytoskeleton and the Membrane 179
III. Actin Filaments Support Nonlinear Ionic Waves 180
IV. Long-Range Spatiotemporal Ionic Waves Along Microtubules 185
V. Dendritic Cytoskeleton Information Processing Model 188
VI. Discussion 190
Acknowledgments 192
References 192
Chapter 9: The Functional Role of Actin Cytoskeleton Dynamics and Signaling 195
I. Introduction 196
II. Studying Actin Cytoskeleton Dynamics 197
A. Actin Cytoskeleton Dynamics in Malignant Cells 197
III. Nongenomic Signaling Pathways Triggering Rapid Actin Reorganization and Regulating Cell Responses 198
A. Example I: Actin Reorganization as a Predominant Event in Nongenomic Steroid Hormone Signaling 198
B. Example II: Actin Reorganization Regulates Nongenomic Transforming Growth Factor-beta Signaling 202
C. Example III: Actin Reorganization and TNF-alpha Signaling 205
D. Example IV: Differential Actin Reorganization as Observed in Opioid Signaling 207
IV. Potential Applications of Altered Actin Dynamics and Signaling in Malignant Cells 209
V. "From Structure to Function" Model for Actin Cytoskeleton Dynamics and Signaling 209
Acknowledgments 210
References 210
Chapter 10: Regulation of the Actin Cytoskeleton by Phospholipids 215
I. Introduction 215
II. General Features of Phosphoinositides and Their Metabolism 216
III. Subcellular Distribution of PI(4,5)P2 and PI(3,4,5)P3 219
IV. Regulation of the Actin Cytoskeleton by Phosphoinositides 221
A. Actin-Dependent Cellular Processes Regulated by Phospholipids 221
V. Conclusions and Future Perspectives 227
References 228
Chapter 11: Lipid Interactions of Cytoskeletal Proteins 235
I. Introduction 236
II. Actin-Associated Proteins 239
A. Proteins Involved in F-Actin Assembly 239
B. Proteins Involved in F-Actin-Membrane Linkage 245
C. Proteins Involved in Actin Cross-Linking 251
D. Myosin Isoforms 252
III. Microtubules and Microtubule-Associated Proteins 253
A. Tubulin 253
B. MAP1B 253
C. Kinesin 254
IV. Intermediate Filaments 255
V. Concluding Remarks 256
A. Selectivity of Cytoskeletal Protein-Lipid Interactions 256
B. Functional Impact of Cytoskeletal Protein-Lipid Interactions 257
C. Open Questions 257
Acknowledgments 258
References 258
Chapter 12: Embryo Morphogenesis and the Role of the Actin Cytoskeleton 265
I. Introduction 266
II. Actin Structures in Morphogenesis 266
A. Actin Protrusions 267
B. Stress Fibers and Actomyosin Cables 270
III. Signals Regulating Actin During Morphogenesis 273
A. Rho Family of Small GTPases 273
B. MAP Kinase Cascades 274
IV. Gastrulation Movements 275
A. Drosophila Gastrulation 275
B. Epiboly in Zebrafish Embryos 275
V. Epithelial Fusion Events 277
A. Drosophila Dorsal Closure 277
B. C. elegans Ventral Enclosure 281
C. Epithelial Fusion Events in Vertebrate Embryonic Development 283
VI. Tugging and Squeezing Movements 284
A. Germ Band Retraction in Drosophila 285
B. C. elegans Elongation 285
C. Heart Folding and Pharynx Development in Vertebrate Embryos 286
VII. Tube Formation 287
A. Epithelial Invagination 287
B. Lumen Formation 289
C. Tube Elongation and Migration 289
VIII. Future Directions 290
A. Initiating and Linking Morphogenetic Episodes 290
B. Mechanical Forces 291
C. Sensing Functions of Actin Protrusions 292
References 293
Chapter 13: Mechanisms of Ion Transport Regulation by Microfilaments 299
I. Introduction 300
II. Role of Actin in Regulation of Transporters at the Plasma Membrane 302
A. NHE3 Regulation at the Cell Surface Requires Interactions with Actin and Other Cytoskeletal and Signaling Proteins 302
B. Actomyosin Contraction Can Both Regulate and Be Regulated by NHE3 304
C. Regulation of NHE3 Activity by Protein Kinases 304
D. Regulation of CFTR by Protein Kinase A 306
III. Mechanisms of Ion Transporter Removal (Endocytosis) from the Plasma Membrane 306
A. Protein Kinase C Inhibits NHE3 by Inducing Endocytosis 306
B. NHE3 Internalization Occurs Through Clathrin-Coated Pits 308
C. Na+K+ ATPase Can Be Regulated by a Clathrin-Mediated Endocytosis 308
IV. Mechanisms of Ion Transporter Delivery to the Cell Surface (Exocytosis) 308
A. Ezrin Regulates NHE3 Translocation from Endosomal Pools to the Plasma Membrane 309
B. Ezrin Activation Represents a Point of Convergence in NHE3 Regulation 310
C. Ezrin Regulates H+K+ ATPase Translocation 312
V. Conclusions 313
Acknowledgments 314
References 314
Chapter 14: Domain-Specific Phosphorylation as a Regulator of Intermediate Filaments 321
I. Introduction 322
II. Regulation of IFs by Phosphorylation 322
III. IF Structure and the Targeting of Phosphorylation 324
IV. Phosphorylation of IFs During Mitosis 327
V. Stress-Induced Phosphorylation of IFs 331
VI. Effects of IF Phosphorylation on Cell Signaling 333
VII. Phosphorylation and Neurofilaments 335
VIII. Dephosphorylation of IFs 337
IX. Conclusions 338
Acknowledgments 339
References 339
Abbreviations and Acronyms 347
Index 349