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Neurobiology of Actin (eBook)

From Neurulation to Synaptic Function
eBook Download: PDF
2010 | 2011
VIII, 282 Seiten
Springer New York (Verlag)
978-1-4419-7368-9 (ISBN)

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This text is an introduction to the interface between the actin cytoskeleton and the myriad of issues fundamental to the understanding of the nervous system. It covers the neurobiology of actin ranging from basic cellular organization and function to the roles of actin in the health and disease states of the nervous system. Its opening chapter presents the fundamental concepts required to appreciate the details of the molecular machinery that regulates actin in a cellular context, setting the stage for the first part of the book which reviews the neurobiology of actin at the cellular level. The latter section of the book then discusses the functions of actin in the context of neurobiological issues ranging from early development to synaptic function and disease states of the nervous system. This text is intended for neuroscientists interested in investigating the actin cytoskeleton in the context of their particular neuroscience research program, and its chapters are cross-referenced in order to assist readers in finding relevant information that is covered in greater depth in other chapters.
This text is an introduction to the interface between the actin cytoskeleton and the myriad of issues fundamental to the understanding of the nervous system. It covers the neurobiology of actin ranging from basic cellular organization and function to the roles of actin in the health and disease states of the nervous system. Its opening chapter presents the fundamental concepts required to appreciate the details of the molecular machinery that regulates actin in a cellular context, setting the stage for the first part of the book which reviews the neurobiology of actin at the cellular level. The latter section of the book then discusses the functions of actin in the context of neurobiological issues ranging from early development to synaptic function and disease states of the nervous system. This text is intended for neuroscientists interested in investigating the actin cytoskeleton in the context of their particular neuroscience research program, and its chapters are cross-referenced in order to assist readers in finding relevant information that is covered in greater depth in other chapters.

Contents 5
Contributors 7
1 Introduction to the Neurobiology of Actin 9
1.1 Preamble 9
1.1.1 Structure of the Book 10
1.1.2 A Primer on Actin and Actin Filaments 10
1.1.3 Additional Suggested Background Sources 13

14 

14 
2 The Neuronal Actin Cytoskeleton and the Protrusion of Lamellipodia and Filopodia 15
2.1 Introduction 15
2.2 Actin Filament Organization in Neuronal Filopodia and Lamellipodia 18
2.3 Polymerization and Turnover of Actin Filaments in Protrusive Structures 20
2.4 Retrograde Flow of Actin Filaments in Protrusive Structures 20
2.5 Integration of Actin Polymerization and Retrograde Flow Determines Protrusive Dynamics 21
2.6 Mechanisms Underlying the Initiation of Filopodia 22
2.7 Relationships Between Filopodial and Lamellipodial Dynamics 24
2.8 Protrusive Dynamics of the Axonal Shaft: Mechanism of Collateral Branch Formation 25
2.9 Inhibition of Protrusion by Repellent Guidance Cues 25
2.10 Localized -Actin mRNA Synthesis as a Regulator of Protrusive Activity 26
2.11 Concluding Remarks 27
References 28
3 Regulation of Actin Filaments During Neurite Extension and Guidance 31
3.1 The Dynamic Neuronal Cytoskeleton 31
3.1.1 Microtubules Provide Support and a Means of Transport 32
3.1.2 Formation of Microtubules in Cells 32
3.1.3 Regulation of Microtubule Organization by MAPs 32
3.1.4 Actin Filaments in Neurons 33
3.1.5 Organization of Actin in Cells 33
3.1.6 Regulation of Actin Filament Organization by ABPs 34
3.1.7 Regulation of Microtubule and Actin Organization and Dynamics by Cytoplasmic Signaling Pathways 35
3.1.8 Microtubule--Actin Interactions Are Important 36
3.1.9 Actin Filaments and Adhesive Contacts 36
3.2 A Mechanism for Neurite Initiation and Growth 36
3.2.1 Organization of Growth Cones and Growth Cone Migration 39
3.2.2 Growth Cone Turning 39
3.2.3 Mechanisms of Branching 40
3.2.4 The Differentiation of Axons and Dendrites: Polarization of Neuronal Form 41
3.3 Regulation of Neuronal Morphogenesis In Vivo 41
3.3.1 Neuronal Migration 41
3.3.2 Neuronal Polarization and the Initial Growth of Axons and Dendrites 42
3.3.3 Axonal Guidance 42
3.3.4 Navigation of Corticofugal Axons 44
3.3.5 Patterning Axonal Distribution Within Targets 46
3.4 Development of Dendrites 47
3.5 Axonal Regeneration 48
References 49
4 Functions of Myosin Motor Proteins in the Nervous System 53
4.1 Introduction 53
4.2 Myosins in Neurons 56
4.2.1 Class I Myosins 56
4.2.2 Class II Myosins 58
4.2.2.1 Myosin II in Neuronal Migration and Cell Adhesion 58
4.2.2.2 Myosin II in Axonal Growth 59
4.2.2.3 Myosin II in Synapse Function 60
4.2.3 Class V Myosins 60
4.2.3.1 Myosin V in Axonal Transport, Growth Cones, and Presynaptic Terminals 61
4.2.3.2 Myosin V in Dendrites and Postsynaptic Function 62
4.2.4 Class VI Myosins 63
4.2.4.1 Myosin VI in Nervous System Development 63
4.2.4.2 Myosin VI in Synaptic Function 64
4.2.5 Classes IX, X, and XVI Myosins 64
4.2.5.1 Class IX Myosins 64
4.2.5.2 Class X Myosins 65
4.2.5.3 Class XVI Myosins 65
4.3 Myosins in Sensory Cells 66
4.3.1 Class I Myosins 66
4.3.2 Class II Myosins 68
4.3.3 Class III Myosins 68
4.3.4 Class V Myosins 68
4.3.5 Class VI Myosins 69
4.3.6 Class VII Myosins 69
4.3.7 Class XV Myosins 70
4.4 Summary and Perspectives 70
References 72
5 MicrotubuleActin Interactions During Neuronal Development 81
5.1 Introduction 81
5.2 MicrotubuleActin Interactions in Developing Neurons 83
5.3 Signaling Cascades Integrate Dynamic Properties of Microtubules and Actin 86
5.4 Integration of Microtubules and Actin via Motor-Driven Forces 87
5.5 Proteins that Interact with Both Microtubules and Actin 90
5.5.1 +TIPs 90
5.5.2 Classical Microtubule-Associated Proteins 93
5.5.3 Non-classical Microtubule-Associated Proteins 97
5.6 Concluding Remarks 99
References 99
6 Working with Actin: Methodological Approaches for the Study of Actin in Neurons 105
6.1 Introduction 105
6.2 Fixation and Immunocytochemistry of Actin in Neurons 107
6.3 Microinjection Microinjection of Labeled Actin or Phalloidi 
110 
6.4 Transfection Transfection of Neurons with 
111 
6.5 Imaging Actin Dynamics in Neurons 114
6.6 Pharmacological Manipulation of Actin 118
6.7 Future Directions for Studying Actin in Neurons 119
References 120
7 Functions of the Actin Cytoskeleton in the Early Embryology of the Nervous System 122
7.1 The Basics and Clinical Significance of Neural Tube Morphogenesis 123
7.2 The Classic Steps of Neural Tube Closure 124
7.3 The Function of the Cytoskeleton in Neurulation 128
7.3.1 Cytoskeletal Regulators that Act Early in Shaping the Neural Plate 130
7.3.2 The Role of the Planar Cell Polarity in Neural Morphogenesis 131
7.3.3 The Role of Actin Regulatory Proteins in Bending and Folding of the Neural Tube 135
7.3.4 Regional Differences in the Requirement for F-Actin 139
7.4 Cilia Formation and Neural Tube Morphogenesis 139
7.5 The Cytoskeleton and Fusion of the Lateral Edges 140
References 141
8 Actin Cytoskeletal Regulation in Neuronal Migration 146
8.1 Introduction 146
8.1.1 Features of Neuronal Locomotion 147
8.1.2 Regulation of Actin Dynamics 152
8.1.3 Peculiarities of Actin Regulation in Neuronal Migration 154
8.1.3.1 Polarization and Centrosome Positioning 154
8.1.3.2 Leading Edge Extension 154
8.1.3.3 Translocation and Extrusion of the Nucleus 156
8.1.3.4 Generation of Motile Force---Microtubule Capture to Cortical Actin and Contractile Elements 157
8.1.3.5 Adhesion and Guidance 158
8.1.3.6 Endocytosis, Actin Regulation, and Neuronal Migration 160
8.2 Concluding Remarks 160
References 161
9 Actin and Neuronal Polarity 168
9.1 Introduction 168
9.2 Model System to Study Neuronal Polarity 169
9.2.1 Neuronal Development In Vivo 169
9.2.2 Dissociated Hippocampal Neurons as Model System to Study Polarity 170
9.2.3 Intrinsic and Extrinsic Regulation of Neuronal Polarity 171
9.3 Which Are the Critical Steps in Polarity Establishment Which Could Be Regulated by Actin 171
9.3.1 First Bud Formation and Control by the Actin Network 171
9.3.2 Stage 2--3 Transition and Actin Control 173
9.3.3 Instructive or Permissive Role of Changes in Actin Dynamics? 174
9.4 Molecular Regulation of the Actin Cytoskeleton During the Establishment of Neuronal Polarity 175
9.4.1 Extrinsic Cues Regulating the Actin Cytoskeleton 176
9.4.2 Intracellular Pathways Which Change Actin Dynamics in Neurons 178
9.4.2.1 Small Rho GTPases and Polarity Control in Neurons 178
9.4.2.2 How Can Rho GTPases Change Actin Dynamics? 179
9.5 Outlook 180
References 181
10 Actin at the Synapse: Contribution to Pre- and Postsynaptic Functions 184
10.1 Presynaptic Roles of Actin 184
10.1.1 Storage 185
10.1.2 Vesicle Docking and Mobilization 186
10.1.3 Priming and Fusion 187
10.1.4 Endocytosis 188
10.2 Postsynaptic Roles of Actin in Inhibitory Synapses 189
10.3 Postsynaptic Roles of Actin in Excitatory Synapses 190
10.4 Roles of Actin in the Motility of Dendritic Spines 191
10.5 Roles of Actin in the Anchoring of AMPA and NMDA Receptors 192
10.5.1 NMDA Receptor Complex 193
10.5.2 AMPA Receptor Complex 194
10.5.3 Master Scaffolding 195
10.6 Roles of Actin in Morphological Changes in Dendritic Spines 195
10.6.1 Rac1/Pak1 Pathway 196
10.6.2 Cdc42/N-WASP/WAVE Pathway 197
10.6.3 RhoA/ROCK/Profilin Pathway 198
10.6.4 SynGAP/Ras Pathway 198
10.7 Roles of Actin in Synaptic Plasticity of Dendritic Spines 198
References 199
11 Actin and Diseases of the Nervous System 208
11.1 Introduction 208
11.1.1 Overview of Actin Dynamics and Superstructures 209
11.1.2 Developmental Disorders 211
11.1.2.1 Neuronal Migration and Cortical Development 211
11.1.2.2 Developmental Disorders of the Neural Crest 213
11.1.2.3 Hereditary Spastic Paraplegias (HSPs) and BMP 215
11.1.3 Post-embryonic Disorders 215
11.1.3.1 Dendritic Spine Dysgenesis and Synaptic Defects 216
11.1.3.2 Dendritic Spine Development and Function 216
11.1.3.3 Long-Term Depression (LTD) and Long-Term Potentiation (LTP) 217
11.1.3.4 Corticobasal Degeneration 218
11.1.3.5 Williams Syndrome 219
11.1.3.6 Mental Illness 220
11.1.3.7 Addiction: Ethanol and Cocaine 221
11.1.3.8 Parkinson's Disease 221
11.1.4 Diseases of mRNA Delivery and Translation 222
11.1.4.1 Overview of mRNA Delivery and Regulation 222
11.1.4.2 Spinal Muscular Atrophy 222
11.1.4.3 Fragile X Syndrome (FXS) and Autism 222
11.1.5 Actin Inclusions and Disease 223
11.1.5.1 ADF/Cofilin--Actin Rods and Other Actin Inclusions 223
11.1.5.2 ADF/Cofilin'Actin Rods and Alzheimer's Disease (AD) 225
11.1.5.3 LIMK1 and Alzheimer's Disease (AD) 227
11.1.5.4 Stroke 228
11.1.5.5 Dystonia with Dementia 228
11.1.5.6 Other Actin-Related Changes Associated with AD 229
11.1.6 Concluding Remarks 229
11.1.6.1 Critical, Often Overlooked Actin Cytoskeletal Properties 229
References 231
12 Signal Transduction Pathways: From Receptor to the Actin Cytoskeleton 242
12.1 Rho GTPase Effectors: Signaling Pathways Induced by Activated GTPases to Regulate Actin 243
12.1.1 RhoA 243
12.1.2 Rac 245
12.1.3 Cdc42 246
12.2 From Receptor to Actin: Growth Cone Guidance Cues Activate Rho GTPases to Induce Cytoskeletal Remodeling 247
12.2.1 Semaphorin Signaling Through Plexin Receptors 247
12.2.2 Slit Signaling Through Robo Receptors 250
12.2.3 Netrin Signaling Through UNC and DCC Receptors 253
12.2.4 Ephrin Signaling Through Eph Receptors 255
12.2.5 Myelin-Derived Growth Inhibitory Proteins Signaling Through the NgR-p75NTR-TROY/TAj Receptor Complex 257
12.3 Spatial Regulation: Orchestration of Rho GTPases in the Growth Cone 260
References 263
Index 271

Erscheint lt. Verlag 4.11.2010
Reihe/Serie Advances in Neurobiology
Advances in Neurobiology
Zusatzinfo VIII, 282 p.
Verlagsort New York
Sprache englisch
Themenwelt Studium 1. Studienabschnitt (Vorklinik) Biochemie / Molekularbiologie
Naturwissenschaften Biologie Humanbiologie
Naturwissenschaften Biologie Zoologie
Technik
Schlagworte Actin • Gallo • Lanier • Neurobiology • receptors
ISBN-10 1-4419-7368-0 / 1441973680
ISBN-13 978-1-4419-7368-9 / 9781441973689
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