Umemori / Hortsch. / Hortsch The Sticky Synapse

Cell Adhesion Molecules and Their Role in Synapse Formation and Maintenance
1. Auflage 2009
ISBN: 978-0-387-92708-4
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Wasserzeichen (»Systemvoraussetzungen)

E-Book, Englisch, 453 Seiten

The molecular mechanisms, which are responsible for the functional differences between the various types of neuronal synapses, have become one of the central themes of modern neurobiology. It is becoming increasingly clear that a misregulation of synaptogenesis and synaptic remodeling and dysfunctional neuronal synapses are at the heart of several human diseases, both neurological disorders and psychiatric conditions. As synapses present specialized cellular junctions between neurons and their target cells, it may not come as a surprise that neural cell adhesion molecules (CAMs) are of special importance for the genesis and the maintenance of synaptic connections. Genes encoding adhesive molecules make up a significant portion of the human genome, and neural CAMs even have been postulated to be a major factor in the evolution of the human brain. These are just some of the many reasons why we thought a book on neural CAMs and their role in establishing and maintaining neuronal synapses would be highly appropriate for summarizing our current state of knowledge. Without question, over the near future, additional adhesive proteins will join the ranks of synaptic CAMs and our knowledge, and how these molecules enable neurons and their targets to communicate effectively will grow.

Dr. Michael Hortsch holds a Diploma degree in Biochemistry from the Free University Berlin and a Ph.D. in Biology from the University of Heidelberg in Germany. While working at the Weizmann Institute in Israel, the European Molecular Biology Laboratory in Heidelberg, and at the University of California at Berkeley he has published on topics such as the mechanism of growth factor receptor activation, the transport of proteins across membranes, and the physiological roles of neuronal cell adhesion molecules during nervous system development. He has been a faculty member of the Department of Cell and Developmental Biology at the University of Michigan in Ann Arbor since 1991. Dr. Hortsch has served on scientific review panels for the National Institutes of Health, the National Science Foundation, and other agencies.   Dr. Hisashi Umemori is a faculty member of the Molecular and Behavioral Neuroscience Institute and of the Department of Biological Chemistry at the University of Michigan Medical School. He worked with Dr. Tadashi Yamamoto at the Institute of Medical Sciences of the University of Tokyo and analyzed intracellular signaling mechanisms that are involved in myelination and in learning and memory. While working with Dr. Joshua R. Sanes at Washington University Medical School and at Harvard University, he identified synaptic organizing molecules that promote synapse formation during nervous system development. Dr. Umemori has received various awards, including a Basil O'Connor Award and a Klingenstein Fellowship Award.    

Autoren/Hrsg.

Umemori, Hisashi

Hortsch., Michael

Hortsch, Michael

Inhaltsverzeichnis

1;Preface;5
2;Contents;6
3;Contributors;8
4;A Short History of the Synapse - Golgi Versus Ramón y Cajal;12
4.1;References;19
5;Cell Adhesion Molecules at the Drosophila Neuromuscular Junction;21
5.1;2.1 Introduction;22
5.2;2.2 CAMs at the NMJ;25
5.2.1;2.2.1 Capricious;25
5.2.2;2.2.2 Connectin;25
5.2.3;2.2.3 Down Syndrome Cell Adhesion Molecule;26
5.2.4;2.2.4 Fasciclin II;26
5.2.5;2.2.5 Fasciclin III;27
5.2.6;2.2.6 Integrins;27
5.2.7;2.2.7 N-Cadherin;28
5.2.8;2.2.8 Neuroglian;28
5.2.9;2.2.9 Toll;29
5.3;2.3 CAMs and Neuromuscular Network Formation;29
5.3.1;2.3.1 Presynaptic Cell Pattern Formation;30
5.3.1.1;2.3.1.1 CAMs and Axon-ECM Adhesion;30
5.3.1.2;2.3.1.2 CAMs and Axon-Axon Adhesion;31
5.3.1.3;2.3.1.3 CAMs and Axon-Muscle Adhesion;31
5.3.2;2.3.2 Postsynaptic Cell Pattern Formation;32
5.4;2.4 CAM-Mediated Intracellular Signaling Activation at the NMJ;34
5.5;2.5 CAMs Mediate FORCES;36
5.6;2.6 CAMs in NMJ Plasticity;37
5.7;2.7 A Two-Step Model for CAM-Mediated NMJ Formation;37
5.7.1;2.7.1 Myopodia Brings CAMs Closer to Navigating Motor Axons;38
5.7.2;2.7.2 CAM-Mediated Postsynaptic Signaling Hub;39
5.8;2.8 CAMs: The Cellular Glue that Holds Our Thoughts Together;41
5.9;References;43
6;Development of the Vertebrate Neuromuscular Junction;48
6.1;3.1 Vertebrate Neuromuscular Junction: A Model Synapse;48
6.2;3.2 Vertebrate Neuromuscular Junction: The Basics;52
6.2.1;3.2.1 Motor Neurons and Their Presynaptic Terminals;53
6.2.2;3.2.2 The Postsynaptic Apparatus;56
6.2.3;3.2.3 Non-myelinating Perisynaptic Schwann Cells;57
6.2.4;3.2.4 The Synaptic Cleft and Basal Lamina;58
6.3;3.3 Morphological Development of the Vertebrate NMJ;61
6.3.1;3.3.1 Synaptic Differentiation;61
6.3.2;3.3.2 Synaptic Maturation and Maintenance;66
6.4;3.4 Trans-synaptic Cues Direct NMJ Formation and Maintenance;68
6.4.1;3.4.1 Historical Perspective;68
6.4.2;3.4.2 Synaptogenic Molecules Within Synaptic BL;69
6.4.3;3.4.3 Agrin;69
6.4.4;3.4.4 Laminins;70
6.4.5;3.4.5 Collagen IV;72
6.4.6;3.4.6 Nidogens;75
6.4.7;3.4.7 Other BL Components Contributing to NMJ Formation and Maintenance;75
6.4.8;3.4.8 Transmembrane Adhesion Molecules Contributing to NMJ Formation and Maintenance;79
6.5;3.5 Vertebrate Neuromuscular Junction: Concluding Remarks;81
6.6;References;81
7;Synapse Formation in the Mammalian Central Nervous System;94
7.1;4.1 Introduction;94
7.2;4.2 Structures and Molecules of CNS Synapses;95
7.2.1;4.2.1 Ultrastructure of CNS Synapses;95
7.2.2;4.2.2 Molecules at CNS Synapses;96
7.2.2.1;4.2.2.1 Presynaptic Scaffold Molecules in the CNS;97
7.2.2.1.1;Munc13-1;97
7.2.2.1.2;RIM1;97
7.2.2.1.3;Bassoon and Piccolo;98
7.2.2.1.4;CASK;98
7.2.2.2;4.2.2.2 Postsynaptic Scaffold Molecules in the CNS;99
7.2.2.2.1;Postsynaptic Scaffold Proteins at the Excitatory Synapse;99
7.2.2.2.1.1;The PSD95/SAP90 Family;99
7.2.2.2.1.2;ProSAP/Shank Family Proteins;99
7.2.2.2.2;Postsynaptic Scaffold Protein at the Inhibitory Synapse;100
7.2.2.2.2.1;Gephyrin;100
7.3;4.3 Synaptogenesis in the CNS;100
7.3.1;4.3.1 Initial Contact of the Axon with its Target and Differentiation of CNS Synapses;100
7.3.2;4.3.2 Maturation and Maintenance of CNS Synapses;102
7.4;4.4 Synaptogenic Molecules in the CNS;103
7.4.1;4.4.1 WNT7a;105
7.4.2;4.4.2 Neurexin/Neuroligin;106
7.4.3;4.4.3 SynCAM (or Nectin-Like Molecules);106
7.4.4;4.4.4 FGF22;107
7.4.5;4.4.5 Narp;107
7.4.6;4.4.6 EphrinB;107
7.4.7;4.4.7 Thrombospondins;108
7.4.8;4.4.8 NGLs, SIRPs, and LRRTMs;108
7.5;4.5 Conclusions;108
7.6;References;109
8;Developmental Axonal Pruning and Synaptic Plasticity;116
8.1;5.1 Introduction;116
8.2;5.2 Stereotyped and Stochastic Axonal Pruning;117
8.3;5.3 Synapse Elimination in the Peripheral Nervous System;118
8.4;5.4 Axonal Pruning in the Central Nervous System;123
8.4.1;5.4.1 Axon Pruning in the Hippocampus: The Development of the Infrapyramidal Bundle;123
8.4.2;5.4.2 Axon Pruning in the Cerebellum: The Regression of Redundant Climbing Fibers;127
8.4.3;5.4.3 Axon Pruning in the Visual System;130
8.5;5.5 Synaptic Plasticity;135
8.6;5.6 Conclusions;140
8.7;References;140
9;Cell Adhesion Molecules in Synaptopathies;150
9.1;6.1 Introduction;150
9.2;6.2 Neuroligins and Neurexins;151
9.3;6.3 Contactin and Contactin-Associated Proteins;156
9.4;6.4 Cadherins and Protocadherins;159
9.5;6.5 CAMs Polymorphisms and the Susceptibility to Psychiatric Conditions;161
9.6;6.6 Conclusions and Perspectives;162
9.7;References;163
10;The Cadherin Superfamily in Synapse Formation and Function;168
10.1;7.1 Introduction;169
10.2;7.2 Classical Cadherins and Catenins;174
10.2.1;7.2.1 Roles in Axon Targeting;175
10.2.2;7.2.2 Roles in Dendrite and Dendritic Spine Morphogenesis;176
10.2.3;7.2.3 Roles in Synapse Formation and Maturation;177
10.2.4;7.2.4 Roles in Synapse Function and Plasticity;178
10.3;7.3 Protocadherins;180
10.3.1;7.3.1 Clustered Protocadherins;180
10.3.2;7.3.2 Fat-Type and 7-Transmembrane Protocadherins;183
10.3.3;7.3.3 delta-Protocadherins;185
10.4;7.4 Concluding Remarks;186
10.5;References;187
11;Nectins and Nectin-Like Molecules in the Nervous System;193
11.1;8.1 Introduction;193
11.2;8.2 General Properties of Nectins and Necls;195
11.3;8.3 Cell-Cell Adhesion Activity of Nectins and Necls;197
11.4;8.4 Nectins Form AJs Cooperatively with Cadherins;198
11.5;8.5 Interactions of Nectins with Other CAMs and a Growth Factor Receptor in Cell Adhesions;201
11.6;8.6 Involvement of Nectins and Cadherins in the Formation of Synapses;202
11.7;8.7 Involvement of Nectins in the Selective Association between Axons and Dendrites;207
11.8;8.8 Possible Roles of Nectins and Cadherins in Synapse Remodeling;207
11.9;8.9 Involvement of Necls in the Formation of Various Types of Cell-Cell Junctions in the Central and Peripheral Nervous Systems;208
11.10;8.10 Conclusions and Perspectives;209
11.11;References;210
12;The Down Syndrome Cell Adhesion Molecule;215
12.1;9.1 Introduction;215
12.2;9.2 Identification of DSCAM Family Members;216
12.3;9.3 General Domain Structure;217
12.4;9.4 DSCAM Molecular Diversity;218
12.5;9.5 Homophilic Interactions;221
12.6;9.6 Branch Segregation and Self-Avoidance;223
12.7;9.7 Tiling;225
12.8;9.8 Non-repulsive DSCAM Functions;226
12.9;9.9 Non-DSCAM Interactions;227
12.10;9.10 Concluding Remarks;228
12.11;References;228
13;Molecular Basis of Lamina-Specific Synaptic Connections in the Retina: Sidekick Immunoglobulin Superfamily Molecules;231
13.1;10.1 Introduction;231
13.2;10.2 The Role of Sdks in Laminar Specificity;232
13.2.1;10.2.1 Laminar Specificity Is a Major Determinant of Synaptic Specificity in the CNS;232
13.2.2;10.2.2 Laminar Organization of the Retina;233
13.2.3;10.2.3 Sdks Mediate Laminar Specificity;234
13.2.4;10.2.4 DSCAMs, Close Relatives of Sdks, Mediate Laminar Specificity;236
13.3;10.3 Molecular and Cellular Properties of Sdks;237
13.3.1;10.3.1 Structure and Expression of Sdks;237
13.3.2;10.3.2 Sdk Ectodomains Mediate Homophilic Adhesion;238
13.3.3;10.3.3 Intracellular Signaling of Sdks;239
13.4;10.4 Conclusions;240
13.5;References;240
14;SYG/Nephrin/IrreC Family of Adhesion Proteins Mediate Asymmetric Cell-Cell Adhesion in Development;243
14.1;11.1 The IrreC/Nephrin/SYG-1 Family of Proteins;243
14.2;11.2 SYG-1 and SYG-2 Encode Synaptic Target Choice of the HSNL Neuron in C. elegans;244
14.3;11.3 Kirre/DUF, IrreC/Roughest, SNS, and Hirbris Mediate Myoblast Fusion in Drosophila;248
14.4;11.4 Kirre/DUF, IrreC/Roughest, SNS, and Hirbris Are Required for Proper Patterning of the Drosophila Eye;249
14.5;11.5 Vertebrate NEPH1 and Nephrin Are Critical Proteins in Kidney Development;249
14.6;11.6 Summary;251
14.7;References;252
15;L1-Type Cell Adhesion Molecules: Distinct Roles in Synaptic Targeting, Organization, and Function;254
15.1;12.1 General Structure and Function of L1-Type Proteins;254
15.2;12.2 Synaptic Functions of L1-Type Cell Adhesion Molecules;257
15.2.1;12.2.1 L1-Type Cell Adhesion Molecules in Learning and Memory;257
15.2.2;12.2.2 L1-Type Cell Adhesion Molecules in Synapse Targeting;259
15.2.3;12.2.3 L1-Type Cell Adhesion Molecules in Synaptogenesis;260
15.2.4;12.2.4 L1-Type Cell Adhesion Molecules in Synaptic Transmission and Signaling;264
15.3;12.3 Conclusions and Outlook;264
15.4;References;265
16;Cell Adhesion Molecules of the NCAM Family and Their Roles at Synapses;271
16.1;13.1 Members of the NCAM Family of Cell Adhesion Molecules;272
16.2;13.2 Structure of NCAM Family Proteins;274
16.3;13.3 Posttranslational Modifications of NCAM Family Proteins;277
16.4;13.4 Extracellular Interaction Partners of NCAM Family Proteins;278
16.5;13.5 Intracellular Interaction Partners of NCAM Family Proteins;282
16.6;13.6 NCAM-Mediated Intracellular Signaling Pathways;284
16.7;13.7 Effects of Extracellular ATP on NCAM Function;284
16.8;13.8 Regulatory Roles for Polysialic Acid in NCAM1 Function;286
16.9;13.9 NCAM Protein in Long-Term Potentiation and Long-Term Depression;289
16.10;13.10 Conclusions;292
16.11;References;293
17;MHC Class I Function at the Neuronal Synapse;306
17.1;14.1 Background;306
17.2;14.2 MHC Class I Expression in Neurons;308
17.2.1;14.2.1 Surface Expression of Neuronal MHC Class I Molecules;310
17.3;14.3 Link to Synaptic Function;311
17.3.1;14.3.1 Synaptic Plasticity in the Developing and Adult Brain;311
17.3.2;14.3.2 Synaptic Elimination in the Axotomized Spinal Cord;312
17.4;14.4 Putative Neuronal MHC Class I Receptors;315
17.5;14.5 Non-synaptic Functions of Neuronal MHC Class I;317
17.5.1;14.5.1 Neuronal Susceptibility to Immune-Mediated Cytotoxicity;317
17.5.2;14.5.2 The Vomeronasal Organ;318
17.6;14.6 Association with Neurological Diseases;319
17.7;References;321
18;Pathfinding Molecules Branch Out: Semaphorin Family Members Regulate Synapse Development;325
18.1;15.1 Introduction;325
18.2;15.2 The Semaphorin Family;326
18.2.1;15.2.1 Discovery and Organization;326
18.2.2;15.2.2 Semaphorin Receptors;327
18.2.3;15.2.3 Biological Functions of Semaphorins and Their Receptors;328
18.3;15.3 Invertebrate Semaphorins Mediate Synapse Development;329
18.4;15.4 Vertebrate Semaphorins in Synapse Formation and Function;330
18.4.1;15.4.1 Class 3 Semaphorins;330
18.4.2;15.4.2 Class 4 Semaphorins;332
18.5;15.5 Conclusions;333
18.6;References;334
19;Ephrins and Eph Receptor Tyrosine Kinases in Synapse Formation;336
19.1;16.1 Introduction;336
19.2;16.2 The Eph Family: Description;337
19.3;16.3 Ephrins Control Neuromuscular Topography and Synapse Formation in the PNS;339
19.4;16.4 Ephs and Ephrins in Synapse Formation in the CNS;341
19.5;16.5 Summary and Future Directions;344
19.6;References;344
20;Neurexins and Neuroligins: A Synaptic Code for Neuronal Wiring That Is Implicated in Autism;349
20.1;17.1 Neurexins: Genes and Proteins Structure;349
20.2;17.2 Neurexin Genes Are Differentially Expressed;350
20.3;17.3 Dystroglycan and Neurexophilin - Neurexin-Interacting Proteins with Unknown Functions;353
20.4;17.4 Neuroligins: Genes and Proteins Structure;354
20.5;17.5 Splicing of Both Neurexins and Neuroligins Determines Affinity and Specificity of Their Interaction;355
20.6;17.6 The Role of Neurexins and Neuroligins in Synapse Formation and Stabilization;357
20.6.1;17.6.1 In Vitro Synapse Formation Assays;357
20.6.2;17.6.2 Intracellular Signaling of Neurexins and Neuroligins;358
20.6.3;17.6.3 The Link Between Cell Adhesion and Synaptic Plasticity;360
20.7;17.7 Neurexin and Neuroligin Gene Polymorphisms in Autism Spectrum Disorders and Mental Retardation;361
20.8;17.8 Conclusions, the Concept of a Synaptic Code and Future Directions;363
20.9;References;364
21;Synaptic Adhesion-Like Molecules (SALMs);368
21.1;18.1 SALM Family Structure and Expression;369
21.2;18.2 SALM-Associated Proteins and Functional Significance;373
21.3;18.3 Homomeric and Heteromeric SALM Interactions;374
21.4;18.4 SALMs Promote Neurite Outgrowth;376
21.5;18.5 SALMs at the Synapse;378
21.6;18.6 Dual Functions for SALMs;379
21.7;References;381
22;The Role of Integrins at Synapses;385
22.1;19.1 Introduction;385
22.2;19.2 Integrins at CNS Synapses;387
22.2.1;19.2.1 Integrins and Synaptic Plasticity;387
22.2.2;19.2.2 Integrins and Memory;388
22.2.3;19.2.3 Integrins Modulate Neurotransmitter Receptors;389
22.2.4;19.2.4 Dendritic Spines and Integrins;390
22.3;19.3 Integrins in the Neuromuscular Junction Synapses;391
22.4;19.4 Role of Integrins in Synaptic Neuropathology;392
22.5;19.5 Concluding Remarks;392
22.6;References;393
23;Extracellular Matrix Molecules in Neuromuscular Junctions and Central Nervous System Synapses;396
23.1;20.1 Introduction;396
23.2;20.2 The Extracellular Matrix of the NMJ;397
23.2.1;20.2.1 Agrin;397
23.2.1.1;20.2.1.1 Alternative Splicing Controls Agrin Activity;399
23.2.1.2;20.2.1.2 Agrin Signal Transduction;400
23.2.1.3;20.2.1.3 Inducing Versus Stabilizing Postsynaptic Sites;400
23.2.1.4;20.2.1.4 The Antagonistic Role of Cholinergic Transmission;401
23.2.2;20.2.2 Laminins at the NMJ;402
23.2.3;20.2.3 Collagens;405
23.2.4;20.2.4 Matrix Components Involved in Synaptic Function;405
23.2.5;20.2.5 Proteases;406
23.2.6;20.2.6 Synapse-Specific Carbohydrates;407
23.2.7;20.2.7 Dystroglycan;408
23.2.8;20.2.8 Growth Factors;409
23.3;20.3 The Extracellular Matrix and CNS Synapses;410
23.3.1;20.3.1 Agrin in the CNS;411
23.3.2;20.3.2 Laminins in the CNS;411
23.3.3;20.3.3 Proteoglycans in the CNS Extracellular Matrix;412
23.3.4;20.3.4 Thrombospondins;413
23.4;20.4 Conclusions;414
23.5;References;415
24;Gap Junctions as Electrical Synapses;422
24.1;21.1 Introduction;422
24.2;21.2 Life History of a Gap Junction;423
24.3;21.3 The First Opening;426
24.4;21.4 Gap Junctions as Sites of Attachment;427
24.5;21.5 Specificity of Junction Formation in the Central Nervous System;429
24.6;21.6 Specificity of Gap Junction Formation Between Neurons;429
24.7;21.7 Why Electrical Coupling?;432
24.8;21.8 Gap Junctions in Development;433
24.9;21.9 A Fixation Artifact?;433
24.10;21.10 Pannexins/Innexins;433
24.11;References;434
25;Index;439