Neurotransmitter release / edited by Hugo J. Bellen.

Format:

Book

Contributor:

Bellen, Hugo J.

Series:

Frontiers in molecular biology ; 23.

Frontiers in molecular biology ; 23

Language:

English

Subjects (All):

Neurotransmitters.

Synapses.

Neural transmission.

Synaptic Transmission--physiology.

Neurotransmitter Agents--physiology.

Receptors, Neurotransmitter.

Signal Transduction.

Medical Subjects:

Synaptic Transmission--physiology.

Neurotransmitter Agents--physiology.

Receptors, Neurotransmitter.

Signal Transduction.

Physical Description:

xviii, 437 pages, 2 unnumbered pages of plates : illustrations ; 25 cm.

Place of Publication:

Oxford ; New York : Oxford University Press, 1999.

Summary:

This book provides extensive background information on neurotransmitter release. It takes a multidisciplinary approach and does not require previous knowledge to most topics discussed. However, the issues addressed are covered in sufficient detail to interest experts in the field. Throughout, emphasis is placed on the rationale by which proteins are assigned specific functions.

Contents:

2. Structure of the synapse 2

2.1 Endocrine cell morphology 3

2.2 Varicosities are non-contacting synapses 3

2.3 The neuromuscular junction 4

2.4 The central nervous system synapse 5

3. Electrophysiological analysis of synaptic transmission 7

3.1 Calcium entry triggers neurotransmitter release 9

3.2 Mobilization, docking, and fusion of synaptic vesicles 10

3.3 Activity-dependent modification of release 12

4. The biochemistry, pharmacology, and genetics of synaptic transmission 13

4.1 The SNARE complex and exocytosis 14

4.2 Recycling of synaptic vesicle membranes 15

4.3 Adhesion molecules in the synapse 20

4.4 Molecular organization of the synapses 22

5. Development of the nerve terminal 24

6. Plasticity of the synapse 25

2 Techniques for elucidating the secretory process: from Ca[superscript 2+] entry to exocytosis / Thomas E. Fisher, Andres F. Oberhauser 34

2. Membrane capacitance measurements with the patch-clamp technique 36

2.1 Capturing the initial stages of the exocytotic fusion pore with the patch-clamp technique 42

3. Amperometric measurements of exocytosis 46

3.1 Monitoring exocytosis using simultaneous measurements of cell membrane capacitance and amperometry 49

4. Ca[superscript 2+] imaging 51

4.1 Fluorescence 51

4.2 Optical measurement 52

4.3 Ca[superscript 2+] indicator dyes 56

4.4 Caged Ca[superscript 2+] compounds 60

4.5 Proteinaceous Ca[superscript 2+] indicators 61

4.6 New imaging techniques 63

5. Imaging of vesicle dynamics 68

5.1 Activity-dependent labelling; the FM dyes 68

5.2 Total internal reflection fluorescence microscopy 71

3 Nerve terminal membrane trafficking proteins: from discovery to function / Christopher D. Hazuka, Davide L. Foletti, Richard H. Scheller 81

2. Discovery of candidate proteins: methodology 83

2.1 Electric organ and rat brain synaptic vesicle purification 83

2.2 Isolation of cDNAs encoding synaptic vesicle proteins 85

2.3 Protein interaction screens for protein discovery 89

2.4 Clues from intracellular trafficking assays 90

2.5 Insights from yeast secretory mutants 92

3. Ascribing possible function to synaptic vesicle-associated proteins 94

4. A model of possible protein interactions underlying synaptic vesicle exocytosis based on protein binding properties 96

5. Insights into the structures of proteins underlying exocytosis 98

5.1 Structures of NSF in the presence and absence of ATP 98

5.2 Conformation of the VAMP/syntaxin/SNAP-25 complex 100

5.3 The structure of the core complex 102

5.4 Structures of the C[subscript 2] domain of synaptotagmin when bound to Ca[superscript 2+] and/or syntaxin 103

6. Current models of protein interaction cascades underlying synaptic vesicle exocytosis 104

6.1 Roles of NSF, [alpha]SNAP, and the SNAREs 104

6.2 The Rab3a cycle 107

6.3 Ca[superscript 2+] regulation of neurotransmitter release 110

6.4 Current model of molecular mechanisms of membrane fusion 111

7. Proteins involved in the organization of synaptic vesicle trafficking in the nerve terminal 111

4 The role of phospholipids in neurosecretion / Thomas F. J. Martin 126

2. Phospholipid composition of biological membranes 126

3. Unique diversity of inositol phospholipids achieved by phosphorylation 128

4. Lipid kinases and transport proteins 128

5. Receptor signalling via phosphoinositide hydrolysis 130

6. Receptor signalling via PI 3-kinase 133

7. Phosphoinositide-binding proteins as effectors for membrane-based signalling 134

8. Inositol phospholipids in membrane traffic 136

9. Perspectives 140

5 Neurotransmitter transporters / David E. Krantz, Farrukh A. Chaudhry, Robert H. Edwards 145

2. Na[superscript +]-and Cl[superscript -]-dependent plasma membrane transporters 147

2.1 GABA transport 147

2.2 Monoamine transport 149

2.3 Glycine and proline transport 150

2.4 Orphan transporters 151

2.5 Transport mechanism 152

2.6 Regulation 157

3. Excitatory amino acid transporters 158

3.1 Identification and isolation 158

3.2 Pharmacology 159

3.3 Mechanism 160

3.4 Physiological role 164

4. Vesicular neurotransmitter transporters 169

4.1 Identification and characterization of transport activity 169

4.2 Vesicular monoamine transport 170

4.3 Vesicular ACh transport 175

4.4 Vesicular amino acid transport 176

4.5 Additional vesicular transport activities 177

4.6 Mechanisms of vesicular neurotransmitter transport 178

4.7 Regulation of vesicular neurotransmitter transport 180

6 Toxins that affect neurotransmitter release / Cahir J. O'Kane, Giampietro Schiavo, Sean T. Sweeney 208

2. Clostridial neurotoxins 208

2.1 The phenomenology of toxicity 209

2.2 Heavy and light chains 209

2.3 Mechanism of light chain action 212

2.4 Factors affecting toxin-target recognition 213

2.5 Do the toxins have other targets or other activities? 214

2.6 Using clostridial neurotoxins to study the function of their targets 217

3. Latrotoxins and excitatory toxins 220

3.1 [alpha]-Latrotoxin 221

4. Calcium channel toxins 223

4.1 Distinguishing the roles of different calcium channels 224

4.2 Using calcium channel toxins to probe synaptic structure 224

5. Phospholipase toxins 225

5.1 Structure-function relationships 225

5.2 Presynaptic activity 226

7 Functional studies of presynaptic proteins at the squid giant synapse / Marie E. Burns, George J. Augustine 237

2. Overview of the squid giant synapse 238

3. Functional studies of presynaptic proteins 240

3.1 Using the squid giant synapse for microinjection studies 240

3.2 Molecular probes of presynaptic proteins 242

3.3 Electron microscopy defines protein action at the level of synaptic vesicle trafficking 254

8 Studying mutants that affect neurotransmitter release in C. elegans / Michael L. Nonet 265

2. C. elegans as a model system 265

2.1 Overview of the nervous system and characteristics of synapses 266

2.2 Identification of genes regulating synaptic transmission 268

2.3 Molecular manipulation of genes 271

2.4 Behavioural and pharmacological analysis 274

2.5 Biochemical and cell biological analysis 275

2.6 Physiological tools 277

3. An overview of C. elegans synaptic mutants 281

3.1 The fusion machinery 281

3.2 Calcium signalling at the nerve terminal 284

3.3 Components of the rab3 pathway 287

3.4 G-protein signalling pathways 287

3.5 Vesicular transporters and ATPases 288

3.6 Endocytosis genes 288

3.7 Other components 290

3.8 Are there additional synaptic mutants to be identified? 290

4. A brief comparison of phenotypic consequences of mutations in different organisms 291

5. Future contributions from the analysis of C. elegans 292

9 Dissecting the molecular mechanisms of neurotransmitter release in Drosophila / Giuseppa Pennetta, Mark N. Wu, Hugo J. Bellen 304

2. Drosophila as a model system 305

2.2 Reverse genetics in Drosophila 307

2.3 Overexpression of proteins 307

2.4 The morphology of the neuromuscular junction or NMJ 308

2.5 Electrophysiological paradigms 310

3. Determining the function of Drosophila proteins in neurotransmitter release 312

3.2 The calcium signalling machinery 312

3.3 The core complex 325

3.4 Proteins that regulate the core complex 332

3.5 Other proteins required for proper neurotransmitter release 338

10 Genetic analysis of neurotransmitter release in mice and humans / Thomas E. Lloyd, Hugo J.

Bellen 352

2. Generating mutant mice and phenotypic analyses 353

2.1 'Knock-out' technology 353

2.2 Preliminary phenotypic analysis 354

2.3 Electrophysiological analysis of knock-out mice 355

2.4 Are mouse knock-outs informative? 358

3. Mutations in synaptotagmin and rab3A: implications for a role in the final steps of exocytosis 360

3.1 Synaptotagmin 360

3.2 Rab3A 363

3.3 Guanine nucleotide dissociation inhibitor 1 368

4. Mutations in synaptic vesicle phosphoproteins 368

4.1 Synapsins 368

4.2 Synaptophysin 372

5. Other mutations in proteins implicated in neurotransmitter release 373

5.1 Neurexin I[alpha] 373

5.2 Sec8 374

6. Mutations in the core complex of proteins implicated in neurotransmitter release 374

6.1 Coloboma mice are deficient in SNAP-25 375

6.2 Williams syndrome patients are haploinsufficient for syntaxin1A 377

11 Synaptic vesicle endocytosis and recycling / Bing Zhang, Mani Ramaswami 389

2. Cell biology of synaptic vescle recycling 390

2.1 Synaptic vesicle recycling: an overview and an alternative view 390

2.2 Kinetics of synaptic vesicle recycling 395

2.3 Distinct pathways of synaptic vesicle endocytosis 397

2.4 Distinct pools of synaptic vesicles 400

2.5 The role of Ca[superscript 2+] in endocytosis 401

3. Molecular mechanisms of synaptic vesicle recycling 403

3.1 Recovery of vesicle proteins and reassembly of endocytic vesicles 407

3.2 Vesicle fission 412

3.3 Post-fission events in synaptic vesicle recycling 417

3.4 Protein-protein interactions in synaptic vesicle endocytosis 418

3.5 Molecular regulation during synaptic vesicle endocytosis 419.

Notes:

Includes bibliographical references and index.

ISBN:

0199637679

0199637660

OCLC:

41476721