Berezin Structure and Function of the Neural Cell Adhesion Molecule NCAM

1. Auflage 2009
ISBN: 978-1-4419-1170-4
Verlag: Springer US
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 663, 434 Seiten

Reihe: Advances in Experimental Medicine and Biology

This book describes recent developments concerning structural, functional and possible therapeutic aspects of one particular CAM, the neural cell adhesion molecule (NCAM).

Autoren/Hrsg.

Berezin, Vladimir

Inhaltsverzeichnis

1;Berezin_Frontmatter.pdf;1
1.1;Preface;5
1.1.1;Contributors;10
2;Berezin_Part-I.pdf;16
3;Berezin_Ch01.pdf;17
3.1;Structural Biology of NCAM;17
3.1.1;Introduction;17
3.1.2;NCAM Belongs to the Immunoglobulin Superfamily of CAMs;18
3.1.3;Architecture of NCAM;18
3.1.4;The Topology of Ig- and Fn3-homology Modules;19
3.1.5;Three-Dimensional Structure of NCAM Ig Modules;21
3.1.6;Three-Dimensional Structures of NCAM Fn3 Modules;24
3.1.7;Models of NCAM-Mediated Homophilic Binding;25
3.1.8;Surface Force Apparatus (SFA) and Atom Force Microscopy Experiments;29
3.1.9;Model of the Extracellular Part of NCAM;30
3.1.10;Perspectives;31
3.1.11;References;33
4;Berezin_Ch02.pdf;37
4.1;Extracellular Protein Interactions Mediated by the Neural Cell Adhesion Molecule, NCAM: Heterophilic Interactions Between NCAM;37
4.1.1;Introduction;38
4.1.1.1;NCAM Isoforms;38
4.1.1.2;NCAM Glycosylation;39
4.1.2;Extracellular Interactions between NCAM and other CAMs;40
4.1.2.1;Interactions between NCAM and the Prion Protein;40
4.1.2.2;Interactions between NCAM and TAG-1;42
4.1.2.3;Interactions between NCAM and L1;44
4.1.3;Interactions between NCAM and Extracellular Matrix Proteins;45
4.1.3.1;Structural Basis for Interactions between NCAM and Heparan Sulfate Proteoglycans;45
4.1.3.2;Biological Significance of Interactions between NCAM and Heparan Sulfate Proteoglycans;47
4.1.3.3;Modulation of Homophilic NCAM Interactions by Heparan Sulfate Proteoglycans;47
4.1.3.4;The Heparan Sulfate Proteoglycans Agrin and Collagen XVIII are NCAM Ligands;48
4.1.3.5;Structural Basis for NCAM Interactions with Chondroitin Sulfate Proteoglycans;50
4.1.3.6;The Chondroitin Sulfate Proteoglycans Neurocan and Phosphacan are Heterophilic NCAM Ligands;50
4.1.3.7;Biological Significance of NCAM Interactions with Chondroitin Sulfate Proteoglycans;52
4.1.3.8;NCAM Interactions with Collagen;53
4.1.3.9;NCAM and Laminin;54
4.1.4;Extracellular Interactions between NCAM and Viruses;54
4.1.5;Concluding Remarks;55
4.1.6;References;57
5;Berezin_Ch03.pdf;68
5.1;Intracelluar Ligands of NCAM;68
5.1.1;Introduction;68
5.1.2;Spectrin, the First Identified Intracellular NCAM-Associated Protein;69
5.1.3;Spectrin’s Function in Recruiting PKCb;70
5.1.4;Spectrin’s Function in Recruiting NMDA Receptor and CaMKIIa;70
5.1.5;NCAM Interacts with the Tyrosine-Kinase Fyn;71
5.1.6;NCAM Binds Not Only Spectrin, But Also Several Other Major Cytoskeletal Proteins;71
5.1.7;Interaction with Signaling Molecules;73
5.1.8;Direct Binding of LANP and PLCg to NCAM;75
5.1.9;MyoNAP, a Novel NCAM-Binding Molecule in Avians;76
5.1.10;Conclusion;76
5.1.11;References;77
6;Berezin_Ch04.pdf;80
6.1;NCAM and the FGF-Receptor;80
6.1.1;Structural Biology of NCAM;80
6.1.2;NCAM Functions;81
6.1.3;Mechanism of the NCAM Homophilic Binding;81
6.1.4;Interaction of NCAM with the FGF-Receptor;83
6.1.5;Mechanism of the FGF-Receptor Activation by NCAM;85
6.1.6;Conclusion;87
6.1.7;References;87
7;Berezin_Ch05.pdf;93
7.1;The Role of ATP in the Regulation of NCAM Function;93
7.1.1;Introduction;93
7.1.2;ATP as a Signaling Molecule in the Nervous System;94
7.1.3;NCAM ecto-ATPase Activity;95
7.1.4;NCAM–FGFR Interaction and ATP;96
7.1.5;ATP and NCAM Ectodomain Shedding;96
7.1.6;ATP and NCAM-Mediated Neurite Outgrowth;98
7.1.7;References;100
8;Berezin_Part-II.pdf;104
9;Berezin_Ch06.pdf;105
9.1;Polysialylation of NCAM;105
9.1.1;Introduction;105
9.1.2;Developmental Regulation of NCAM Polysialylation;106
9.1.3;Re-expression of Polysia in Tumors;107
9.1.4;PolySia Biosynthesis;108
9.1.5;Phenotype of Polysia-deficient Mice;112
9.1.6;Future Directions;113
9.1.7;References;114
10;Berezin_Ch07.pdf;120
10.1;Structural Basis for the Polysialylation of the Neural Cell Adhesion Molecule;120
10.1.1;Introduction;120
10.1.2;Polysialic Acid: An Important Regulator of NCAM-dependent and NCAM-independent Adhesion;120
10.1.3;Polysialylation of NCAM: A Protein Specific Modification;122
10.1.4;NCAM Domains Required for Polysialylation;123
10.1.5;The Unique b Sandwich Structure of NCAM FN1: The Role of an Acidic Surface Patch and Novel a-Helix in NCAM Polysialylatio;124
10.1.6;Are Interdomain Interactions Critical for Polysialylation of the Ig5 N-glycans?;127
10.1.7;Reconstitution of PolyST Recognition and Polysialylation of an Unpolysialylated NCAM-OCAM Chimeric Protein;128
10.1.8;A Model of PolyST-NCAM Interaction;130
10.1.9;Future Directions;130
10.1.10;References;131
11;Berezin_Ch08.pdf;136
11.1;The Role of PSA-NCAM in Adult Neurogenesis;136
11.1.1;Introduction;136
11.1.2;PSA-NCAM Expression in Adult Neurogenic Sites;137
11.1.3;Putative Functions of PSA-NCAM in Adult Neurogenesis;138
11.1.3.1;Neuronal Precursor Migration;138
11.1.3.2;Survival of Newly Generated Neurons;140
11.1.3.3;Neuronal Precursor Differentiation;141
11.1.4;Concluding Remarks;142
11.1.5;References;143
12;Berezin_Ch09.pdf;146
12.1;Use of PSA-NCAM in Repair of the Central Nervous System;146
12.1.1;Introduction;146
12.1.2;Polysialic Acid and Global Regulation of Cell Interactions;146
12.1.3;PSA-Induced Tissue Plasticity;147
12.1.3.1;PSA Promotes Precursor Cell Migration;148
12.1.3.2;PSA Facilitates Development of Neuronal Projections;148
12.1.4;Use of PSA Gain-of-Function to Promote Adult Tissue Repair;148
12.1.4.1;Regeneration of Damaged CNS Axons;149
12.1.4.2;Delivery of Neural Progenitors to a Brain Injury;151
12.1.5;Summary and Prospects;153
12.1.6;References;154
13;Berezin_Part-III.pdf;157
14;Berezin_Ch10.pdf;158
14.1;Signaling Pathways Involved in NCAM-Induced Neurite Outgrowth;158
14.1.1;Introduction;158
14.1.2;The MAPK Pathway;160
14.1.3;Fibroblast Growth Factor Receptor;160
14.1.4;Nonreceptor Tyrosine Kinases, Fyn and FAK;162
14.1.5;Rafts and Cytoskeletal Components;163
14.1.6;Intracellular Ca2+ and Activation of CaMKII;166
14.1.7;PKC;167
14.1.8;cAMP and PKA;168
14.1.9;The cGMP Pathway;168
14.1.10;PI3K and Akt;169
14.1.11;CREB;169
14.1.12;Concluding Remarks;170
14.1.13;References;171
15;Berezin_Ch11.pdf;176
15.1;Role of the Growth-Associated Protein GAP-43 in NCAM-Mediated Neurite Outgrowth;176
15.1.1;Introduction;176
15.1.2;Role of NCAM in the Nervous System;176
15.1.3;Role of GAP-43 in Remodeling of the Actin Cytoskeleton and Neurite Outgrowth;177
15.1.4;Involvement of GAP-43 in Neuronal Adhesion and NCAM-Mediated Neurite Outgrowth;178
15.1.5;Role of GAP-43 Phosphorylation in NCAM-Mediated Neurite Outgrowth;179
15.1.6;FGFR Function Is Required for NCAM-Stimulated GAP-43 Phosphorylation;180
15.1.7;PSA-NCAM and GAP-43 Are Coexpressed as Plasticity-Promoting Molecules: Possible Signaling Mechanisms Linking PSA-NCAM to GAP-43;180
15.1.8;Differential Role of NCAM Isoforms in GAP-43-Mediated Neurite Outgrowth;181
15.1.9;Functional Complex of NCAM-180 with GAP-43 and Spectrin;182
15.1.10;Open Question: Fyn/RPTPa Association with NCAM-180/Spectrin/GAP-43 Complex;183
15.1.11;NCAM and Growth-Associated Proteins BASP1 and MARCKS;183
15.1.12;References;185
16;Berezin_Ch12.pdf;190
16.1;The Neural Cell Adhesion Molecule NCAM and Lipid Rafts;190
16.1.1;Introduction;190
16.1.2;Lipid Rafts;191
16.1.3;Localisation of NCAM Inside and Outside Lipid Rafts;193
16.1.4;Localisation of NCAM Signalling Partners in Lipid Rafts and the Importance of Lipid Rafts for NCAM Signalling;195
16.1.4.1;The FGF Receptor;195
16.1.4.2;Fyn Kinase and RPTPa;195
16.1.4.3;Spectrin;197
16.1.4.4;Growth-Associated Protein-43;199
16.1.5;Conclusions and Perspectives;201
16.1.6;References;201
17;Berezin_Ch13.pdf;206
17.1;The Neural Cell Adhesion Molecule and Epidermal Growth Factor Receptor: Signaling Crosstalk;206
17.1.1;Introduction;206
17.1.2;Interactions Between NCAMs and the EGF Receptor in Drosophila;207
17.1.3;The Mammalian EGF Receptor: Regulation and Role in the Nervous System;208
17.1.4;Crosstalk Between Neuronal CAMs and EGF Receptor Signaling in Mammalian Cells;210
17.1.5;Conclusions and Perspectives;212
17.1.6;References;213
18;Berezin_Part-IV.pdf;217
19;Berezin_Ch14.pdf;218
19.1;Biosynthesis of NCAM;218
19.1.1;Introduction;218
19.1.2;Transcription of NCAM Gene;219
19.1.3;Alternative Splicing of NCAM Gene;219
19.1.4;Biosynthesis and Intracellular Transport of NCAM Molecule;220
19.1.5;Posttranslational Modifications: Glycosylation, Sulfation, Phosphorylation, and Palmitoylation;221
19.1.5.1;N-Linked Glycosylation of NCAM;222
19.1.5.2;O-Linked Glycosylation of NCAM;222
19.1.5.3;NCAM Polysialylation;222
19.1.5.4;The HNK-1/L2 Epitope on NCAM;223
19.1.5.5;NCAM Phosphorylation;223
19.1.5.6;NCAM Sulfation;223
19.1.5.7;NCAM Palmitoylation;224
19.1.6;Cellular Distribution of NCAM;224
19.1.7;NCAM Expression in Various Organs and Tissues During Development;224
19.1.8;Conclusions;226
19.1.9;References;226
20;Berezin_Ch15.pdf;231
20.1;Soluble NCAM;231
20.1.1;Introduction;231
20.1.2;Characterization of Soluble NCAM;232
20.1.3;The Source of Soluble NCAM;233
20.1.3.1;Secretion;233
20.1.3.2;Enzymatic Cleavage of the Extracellular Domain;233
20.1.3.3;Detached NCAM-Containing Membrane Fragments;235
20.1.4;Biological Effect of Soluble NCAM;235
20.1.4.1;In Vitro;235
20.1.4.2;In Vivo;237
20.1.5;Soluble NCAM in Disease;238
20.1.5.1;Schizophrenia;240
20.1.5.2;Mood Disorders;240
20.1.5.3;Neurodegenerative Disorders;241
20.1.5.4;Cancer;241
20.1.5.5;Others Disorders;242
20.1.6;Summary;242
20.1.7;References;243
21;Berezin_Part-V.pdf;247
22;Berezin_Ch16.pdf;248
22.1;Role of NCAM in Spine Dynamics and Synaptogenesis;248
22.1.1;Introduction;248
22.1.1.1;Adhesion Molecules and Synaptogenesis;249
22.1.1.2;Role of NCAM and PSA-NCAM in Synaptic Function and Plasticity;250
22.1.1.3;Role of PSA-NCAM in Synaptogenesis;251
22.1.1.4;Dynamic Aspect of Spine Turnover and Synapse Formation;252
22.1.1.5;Regulation of Spine Stability and Function by PSA-NCAM/NCAM Ratio;255
22.1.2;Conclusion;256
22.1.3;References;256
23;Berezin_Ch17.pdf;260
23.1;NCAM in Long-Term Potentiation and Learning;260
23.1.1;Introduction;260
23.1.2;NCAM in Learning and LTP;262
23.1.3;NCAM Expression and Localization in Synaptic Plasticity;265
23.1.4;PSA-NCAM in Synaptic Plasticity;266
23.1.5;Synaptic Plasticity in NCAM-Deficient Mice;267
23.1.6;NCAM in Synaptogenesis;268
23.1.7;Concluding Remarks;269
23.1.8;References;270
24;Berezin_Ch18.pdf;274
24.1;Role of NCAM in Emotion and Learning;274
24.1.1;Introduction;274
24.1.2;General Features of NCAM in the Central Nervous System: Molecular Structure and Function;274
24.1.3;NCAM and Emotion;275
24.1.4;NCAM in Learning: Functional Studies;281
24.1.5;NCAM in Learning: Correlative Studies;283
24.1.6;PSA-NCAM in Learning;284
24.1.7;NCAM and PSA-NCAM: Sensitive Indices of “Emotional Learning”;285
24.1.8;Mechanisms Related to NCAM Actions on Learning;293
24.1.9;References;294
25;Berezin_Part-VI.pdf;300
26;Berezin_Ch19.pdf;301
26.1;NCAM in Neuropsychiatric and Neurodegenerative Disorders;301
26.1.1;Introduction;301
26.1.2;Schizophrenia;304
26.1.3;Mood Disorders: Bipolar Disorder;306
26.1.4;Mood Disorders: Depression;307
26.1.5;Anxiety Disorders;309
26.1.6;Alzheimer’s Disease;310
26.1.7;Future Directions;311
26.1.8;References;312
27;Berezin_Ch20.pdf;320
27.1;Neural Cell Adhesion Molecule in Cancer: Expression and Mechanisms;320
27.1.1;Introduction;320
27.1.2;NCAM in Human Cancer: An Overview;321
27.1.2.1;Brain Tumors;322
27.1.2.2;Myeloma;322
27.1.2.3;Acute Myeloid Leukemia;323
27.1.2.4;Gastrointestinal Cancers;323
27.1.2.5;Thyroid Cancer;324
27.1.2.6;Small Cell Lung Cancer;325
27.1.3;How Does NCAM Modulate Tumor Development?;325
27.1.3.1;NCAM and Tumor–Microenvironment Interactions: The Rip1Tag2 Model;325
27.1.3.2;NCAM and Tumor Angiogenesis;327
27.1.3.3;The NCAM–FGFR Crosstalk;328
27.1.4;Perspectives;330
27.1.5;References;330
28;Berezin_Part-VII.pdf;335
29;Berezin_Ch21.pdf;336
29.1;NCAM Mimetic Peptides: An Update;336
29.1.1;Introduction;336
29.1.2;Ectodomain Structure of NCAM and Natural Extracellular Interaction Partners;342
29.1.3;Artificial NCAM-Binding Peptides;342
29.1.3.1;C3;342
29.1.3.2;NBP10;343
29.1.3.3;ENFIN2 and ENFIN11;344
29.1.4;Synthetic NCAM-Derived Peptides Targeting NCAM;344
29.1.4.1;P2;344
29.1.4.2;P1-B;345
29.1.4.3;P-3-G;345
29.1.4.4;P-3-DE;345
29.1.5;Synthetic NCAM-Derived Peptides Targeting Heterophilic Ligands of NCAM;345
29.1.5.1;FGL;346
29.1.5.2;FRM;347
29.1.5.3;DekaCAM;347
29.1.5.4;BCL;347
29.1.5.5;Encamin Peptides;348
29.1.5.6;HBP;348
29.1.6;Conclusions;348
29.1.7;References;349
30;Berezin_Ch22.pdf;353
30.1;Synthetic NCAM-Derived Ligands of the Fibroblast Growth Factor Receptor;353
30.1.1;Introduction;353
30.1.2;NCAM Interactions with FGFR;354
30.1.3;Structural Basis for the Interaction Between NCAM and FGFR;355
30.1.4;FGL, a Synthetic FGFR-Ligand Derived from the Second NCAM FN3 Module;356
30.1.5;FGL-Induced Intracellular Signaling;357
30.1.6;Cellular Responses to FGL In Vitro;358
30.1.7;Effects of FGL In Vivo;359
30.1.8;BCL, a Synthetic FGFR Ligand Derived from the Second NCAM FN3 Module;360
30.1.9;FRM, a Synthetic FGFR Ligand Derived from the First NCAM FN3 Module;361
30.1.10;DekaCAM, a Synthetic NCAM and FGF10-Derived FGFR Ligand;362
30.1.11;Mechanism of FGFR Activation by the Peptides;363
30.1.12;Different NCAM-Derived FGFR Ligands Induce Differential Responses;364
30.1.13;Conclusions and Future Directions;366
30.1.14;References;366
31;Berezin_Ch23.pdf;371
31.1;Dendritic Spine and Synapse Morphological Alterations Induced by a Neural Cell Adhesion Molecule Mimetic;371
31.1.1;Introduction;371
31.1.1.1;NCAM Involvement in Synapse Formation;371
31.1.1.2;NCAM Involvement in Memory;372
31.1.2;What Is the Mode of Action of NCAM at the Cellular/Synaptic Level?;372
31.1.3;How Does NCAM Influence Synaptic and Dendritic Morphology?;373
31.1.3.1;Aged Rats;373
31.1.3.2;Spine Volume, and Percentage Distribution of Synapse on Spine Types;373
31.1.3.3;Curvature Changes;374
31.1.3.4;Volume and Surface Area of Endososmes/Multivesicular Bodies;375
31.1.4;Does FGL Exert a Similar Effect on Younger Animals?;377
31.1.5;The Mechanism of NCAM Action at the Synaptic Level?;377
31.1.5.1;Multivesicular Bodies and Clathrin Coated Pits;378
31.1.6;References;379
32;Berezin_Part-VIII.pdf;382
33;Berezin_Ch24.pdf;383
33.1;Fasciclin II: The NCAM Ortholog in Drosophila melanogaster;383
33.1.1;Introduction;383
33.1.2;Alternative Splicing and Posttranslational Modifications;385
33.1.3;Fasciclin II Expression;386
33.1.4;Cell Adhesion Mechanism;387
33.1.5;Proneural Functions;387
33.1.6;Axon Growth and Guidance;388
33.1.7;Activation of EGFR and FGFR;388
33.1.8;Synaptic Functions;390
33.1.9;References;392
34;Berezin_Ch25.pdf;398
34.1;The Neural Cell Adhesion Molecule NCAM2/OCAM/RNCAM, a Close Relative to NCAM;398
34.1.1;Cell Adhesion Molecules in the Nervous System;399
34.1.2;The Identification of NCAM2;399
34.1.3;Isoforms and Protein Structure of NCAM2;400
34.1.4;Extracellular Posttranslational Modifications of NCAM2;403
34.1.4.1;Glycosylation;403
34.1.5;Intracellular Posttranslational Modifications of NCAM2;406
34.1.5.1;Acetylation;406
34.1.5.2;Phosphorylation;407
34.1.6;Expression of NCAM2;407
34.1.7;Homophilic NCAM2 Interactions;408
34.1.8;Heterophilic Binding Partners of NCAM2;408
34.1.9;Functions;409
34.1.9.1;NCAM2 in the Olfactory System;409
34.1.9.2;NCAM2 in Down Syndrome, Autism, and Cancer;410
34.1.10;Concluding Remarks;411
34.1.11;References;412
35;Berezin_Part-IX.pdf;416
36;Berezin_Ch26.pdf;417
36.1;Honoring Dr. Elisabeth Bock;417
36.1.1;References;419
37;Berezin_Backmatter.pdf;421