Larsson Cell Fusions

Regulation and Control
1. Auflage 2010
ISBN: 978-90-481-9772-9
Verlag: Springer Netherlands
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 436 Seiten

Cell fusions are important to fertilization, placentation, development of skeletal muscle and bone, calcium homeostasis and the immune defence system. Additionally, cell fusions participate in tissue repair and may be important to cancer development, progression and therapy. A large number of factors regulate cell fusions, including receptors and ligands, membrane domain organizing proteins, proteases, signaling molecules and fusogenic proteins that bring membranes close together. In the present volume, we interrogate what mechanisms that may be important to cell fusions in mammals and what mechanisms that may be shared with lower organisms and viruses. Additionally, the importance of cell fusions to the pathogenesis as well as treatment of diseases is addressed.

Autoren/Hrsg.

Larsson, Lars-Inge

Inhaltsverzeichnis

1;Preface;5
2;Contents;7
3;Contributors;9
4;1 Regulation and Control of Cell--Cell Fusions;13
4.1;References;20
5;2 Retroviruses and Cell Fusions: Overview;22
5.1;2.1 Introduction;24
5.2;2.2 Basic Features of the Retroviral Fusion Machinery;26
5.2.1;2.2.1 Entry;26
5.2.2;2.2.2 Receptors;26
5.2.3;2.2.3 Interference;27
5.2.4;2.2.4 Membrane Fusion;28
5.2.5;2.2.5 Fusion Inhibitors;30
5.2.6;2.2.6 The Significance of the Coiled Coil Structures;30
5.2.7;2.2.7 Control Mechanism for Fusion Activation;31
5.2.8;2.2.8 Retroviral Fusion of Cells;32
5.3;2.3 Fusion Control in Different Groups of Retroviruses;33
5.4;2.4 Endogenous Retroviruses and Cell Fusion;37
5.4.1;2.4.1 Origin and Classification of Endogenous Retroviruses;37
5.4.2;2.4.2 Evolutionary View of HERV env Genes;38
5.4.3;2.4.3 Structural Composition of HERV Envelope Proteins;42
5.5;2.5 Conclusion;43
5.6;References;44
6;3 Retroviral Membrane Fusions: Regulation by Proteolytic Processing and Cellular Factors;51
6.1;3.1 Introduction;53
6.2;3.2 Membrane Fusion by Retroviral Env Protein;54
6.2.1;3.2.1 Cell Surface Receptor;54
6.2.2;3.2.2 Membrane Fusion Mechanism;56
6.3;3.3 Regulation of Retroviral Membrane Fusion by Proteolytic Processing;57
6.3.1;3.3.1 Processing of Precursor Env Polyprotein;57
6.3.2;3.3.2 R Peptide Cleavage;58
6.3.3;3.3.3 Syncytium Formation in XC Cells by MLV;59
6.3.4;3.3.4 Mechanism of R Peptide to Inhibit Membrane Fusion;59
6.3.5;3.3.5 Cleavage by Cathepsin Proteases;60
6.4;3.4 Regulation of Retroviral Membrane Fusion by Cellular Factors;62
6.4.1;3.4.1 Lipid Raft;62
6.4.2;3.4.2 Cell Adhesion Molecules;63
6.4.3;3.4.3 Cytoskeleton-Associated Molecules;64
6.5;3.5 Conclusion;65
6.6;References;65
7;4 A Comparative Portrait of Retroviral Fusogens and Syncytins;72
7.1;4.1 Introduction;75
7.2;4.2 Contribution of the Envelope to the Retroviral Life Cycle;77
7.2.1;4.2.1 Synthesis of Env Glycoprotein and Viral Assembly;78
7.2.1.1;4.2.1.1 Synthesis and Maturation of Env Glycoprotein;80
7.2.1.2;4.2.1.2 Cellular Localization of Env Glycoprotein and Viral Assembly;82
7.2.1.3;4.2.1.3 Fusion Competency;84
7.2.2;4.2.2 Virus-Host Cell Membrane Fusion: A Multistep Mechanism;84
7.2.2.1;4.2.2.1 Receptor Binding and Peptide Fusion Liberation;86
7.2.2.2;4.2.2.2 Pore Formation and Fusion of the Target Membranes;88
7.2.3;4.2.3 Rous Meets Mendel;89
7.3;4.3 Syncytins and CellCell Fusion;92
7.3.1;4.3.1 Integration, Domestication Steps and Biological Functions of Endogenous Viral Glycoproteins;94
7.3.1.1;4.3.1.1 Integration Dating and Orthologues;94
7.3.1.2;4.3.1.2 Endogenous Retrovirus Envelopes Are Expressed in the Placenta and in the Testis Suggesting a Direct Involvement in Developmental Process;96
7.3.1.3;4.3.1.3 Biological Function of ERVs Envelopes;96
7.3.2;4.3.2 Fusion Mechanism and Receptor Recognition;98
7.3.2.1;4.3.2.1 Maturation;98
7.3.2.2;4.3.2.2 Receptor Binding;101
7.3.2.3;4.3.2.3 Incorporation in Particles;102
7.3.3;4.3.3 Retroviral Envelopes Are Involved in the Placenta Development;103
7.3.3.1;4.3.3.1 Envelope and Receptor Localization Throughout Mammalian Gestation;103
7.3.3.2;4.3.3.2 Splicing Strategy, Transcription Factors and Epigenetic Control;106
7.3.3.3;4.3.3.3 Additional Factors;108
7.3.4;4.3.4 Syncytin-1 Expression Outside of Its Privileged Tissue;111
7.4;4.4 Conclusion;112
7.5;References;113
8;5 Syncytins: Molecular Aspects;125
8.1;5.1 Cell Fusion in the Placenta;127
8.1.1;5.1.1 Development of the Placenta;127
8.1.2;5.1.2 Human Syncytin-1;128
8.1.3;5.1.3 Human Syncytin-2;129
8.1.4;5.1.4 Mouse Syncytin-A and -B;130
8.2;5.2 Structure and Functional Studies of Syncytins;130
8.2.1;5.2.1 Biosynthesis of Syncytins;131
8.2.2;5.2.2 Functional Domains and Motifs in Syncytins;132
8.2.3;5.2.3 Syncytin Receptors;134
8.2.4;5.2.4 Mechanism of Membrane Fusion;135
8.3;5.3 Regulation of Syncytin Expression;136
8.3.1;5.3.1 GCM1 Regulation of Syncytin-1 and -2 Gene Expression;136
8.3.2;5.3.2 Regulation of GCM1 Activity;137
8.3.3;5.3.3 Epigenetic Regulation of Syncytin-1 and -2 Gene Expression;138
8.4;5.4 Syncytins and Disease;139
8.4.1;5.4.1 Syncytins in Placental Disorders;139
8.4.2;5.4.2 Syncytin-1 in Malignancies;140
8.4.3;5.4.3 Syncytin-1 in Neurological Diseases;141
8.5;5.5 Conclusion;142
8.6;References;143
9;6 Role of the Actin Cytoskeleton Within FuRMAS During Drosophila Myoblast Fusion and First Functionally Conserved Factors in Vertebrates;146
9.1;6.1 Introduction to the Cell Biology and Topology of Myoblast Fusion in Drosophila;148
9.1.1;6.1.1 Founder Cells, Fusion-Competent Myoblasts, Progenitors and Myofibres;149
9.1.2;6.1.2 Two Phases of Myoblast Fusion;150
9.2;6.2 Pre-fusion Complexes Form at Opposing Membranes, the Membranes Vesiculate, and FCMs Are Integrated into the Growing Myotube;152
9.2.1;6.2.1 Electron-Dense Vesicles and the Pre-fusion Complex;154
9.2.2;6.2.2 Electron-Dense Plaques and Vesiculating Membranes;154
9.3;6.3 Cell Adhesion and Signalling Cascades;155
9.3.1;6.3.1 Cell Adhesion;157
9.3.2;6.3.2 Duf/Kirre Very Likely Acts via Rolling Pebbles in FCs and Growing Myoblasts;158
9.3.3;6.3.3 Signalling on the FCM Side;159
9.4;6.4 Actin Regulation at the Site of Adhesion During Drosophila Myoblast Fusion;160
9.4.1;6.4.1 Molecular Mechanisms of F-Actin Regulation at the Site of Drosophila Myoblast Fusion;161
9.4.2;6.4.2 Possible Roles for Arp2/3-Based F-Actin Formation at the Site of Drosophila Myoblast Fusion;163
9.4.3;6.4.3 Actin Regulation During Vertebrate Myoblast Fusion;166
9.5;6.5 The FuRMAS Model and the Topology of Myoblast Fusion;168
9.5.1;6.5.1 Fusion Pores, Membrane Vesiculation and the Size of Cytoplasmic Continuities;169
9.5.2;6.5.2 FuRMAS as Signalling Centres;170
9.6;6.6 Outlook;172
9.7;References;172
10;7 Role of CD9 in Sperm-Egg Fusion and Its General Role in Fusion Phenomena;178
10.1;7.1 Introduction;179
10.2;7.2 Sperm-Egg Fusion in Fertilization;180
10.3;7.3 CD9 and Its Role in Cell Function;182
10.4;7.4 Tetraspanin;183
10.5;7.5 Tetraspanin as a Component of Exosomes;185
10.6;7.6 Lessons from Living Eggs;185
10.7;7.7 Membrane Fusion and Exosomes;186
10.8;References;189
11;8 Gamete Binding and Fusion;192
11.1;8.1 Introduction;194
11.2;8.2 Membrane Fusion Events During Acrosomal Exocytosis;195
11.3;8.3 Essential Role of CD9 in Sperm-Egg Binding;196
11.4;8.4 IZUMO-the Candidate Sperm Partner of Oolemma Tetraspanins;198
11.5;8.5 IntegrinDisintegrin Interactions in Sperm-Egg Binding;199
11.6;8.6 Eqatorin MN9 and other Sperm Surface Ligands Implicated in Sperm-Oolemma Fusion;201
11.7;8.7 Conclusions;202
11.8;References;204
12;9 Mechanisms Regulating Human Trophoblast Fusion;209
12.1;9.1 Introduction;211
12.2;9.2 Human Placenta and Villous Trophoblast;211
12.3;9.3 Regulators of Trophoblast Fusion;212
12.3.1;9.3.1 Cytokines, Growth Factors and Trophoblast Fusion;212
12.3.2;9.3.2 Protein Kinases, Transcription Factors and Trophoblast Fusion;212
12.3.3;9.3.3 The Phosphatidylserine Flip and Trophoblast Fusion;214
12.3.4;9.3.4 Caspase 8 Activity and Trophoblast Fusion;215
12.3.5;9.3.5 Fusogenic Proteins and Trophoblast Fusion;217
12.4;9.4 Pitfalls in Dealing with Trophoblast Fusion In Vitro;218
12.4.1;9.4.1 Phenotype of Isolated Primary Trophoblasts;218
12.4.2;9.4.2 The Use of ß-hCG to Determine the Extentof Trophoblast Fusion;219
12.5;9.5 Conclusions;220
12.6;References;220
13;10 Macrophage Fusion: The Making of a New Cell;224
13.1;10.1 Macrophage Multinucleation;226
13.1.1;10.1.1 What Are Macrophages?;226
13.1.2;10.1.2 Osteoclasts and Giant Cells;227
13.1.3;10.1.3 Cellular Fusogens;229
13.1.4;10.1.4 Macrophage Fusion Machinery;230
13.1.5;10.1.5 Recognition of Self;232
13.2;10.2 Conclusion;234
13.3;References;235
14;11 Molecules Regulating Macrophage Fusions;237
14.1;11.1 Overall;239
14.1.1;11.1.1 Cell--Cell Fusion in Macrophages and Osteoclasts;239
14.2;11.2 Macrophage and Osteoclast CellCell Fusion;240
14.2.1;11.2.1 MGCs;240
14.2.2;11.2.2 FBGCs as MGCs;240
14.2.3;11.2.3 Phagocytosis and ER-Mediated Cell--Cell Fusion;241
14.2.4;11.2.4 Osteoclasts;241
14.3;11.3 Differentiation of Osteoclasts;242
14.3.1;11.3.1 Differentiation of Osteoclasts and Cell--Cell Fusion Is Induced at the Last Stage of Differentiation;242
14.3.2;11.3.2 Anchorage-Dependent Osteoclast Cell--Cell Fusion;242
14.3.3;11.3.3 Molecular Understanding of Cell--Cell Fusion in Macrophages and Osteoclasts;243
14.3.4;11.3.4 The Role of Cell--Cell Fusion: Described in Gene Targeted and Transgenic Mice;245
14.3.5;11.3.5 Transcriptional Regulation of Cell--Cell Fusion in Osteoclasts and MGCs;246
14.4;11.4 Future Directions;247
14.4.1;11.4.1 Fusion of Macrophages with Cancer and Somatic Cells;247
14.5;11.5 Concluding Remarks;248
14.6;References;248
15;12 Current Progress Towards Understanding Mechanisms of Myoblast Fusion in Mammals;253
15.1;12.1 Introduction;254
15.2;12.2 Biochemical Requirements for Myoblast Fusion;254
15.3;12.3 Methodology for Studying Myoblast Fusion;255
15.3.1;12.3.1 In Vitro Models;255
15.3.2;12.3.2 In Vivo Studies;257
15.4;12.4 Current Areas of Research in Myoblast Fusion;257
15.4.1;12.4.1 Elongation and Membrane Alterations;258
15.4.2;12.4.2 Migration;259
15.4.3;12.4.3 Muscle Cell Recognition/Adhesion;260
15.4.4;12.4.4 Actin Dynamics and Integrin Function;261
15.4.5;12.4.5 Regulation of Cell Fusion with Nascent Myotubes;262
15.4.5.1;12.4.5.1 Nuclear Factor of Activated T Cells: Modulators and Effectors;263
15.4.5.2;12.4.5.2 Additional Molecules that Control Fusion with Nascent Myotubes;264
15.5;12.5 Future Prospects;265
15.6;References;266
16;13 The Endogenous Envelope Protein Syncytin Is Involved in Myoblast Fusion;270
16.1;13.1 Introduction;271
16.2;13.2 Syncytin-1 and Myoblast Fusion;272
16.3;13.3 How Does Syncytin-1 Mediate Fusion?;275
16.4;13.4 Conclusions and Perspectives;276
16.5;References;276
17;14 Cell Fusion and Stem Cells;279
17.1;14.1 Introduction;281
17.1.1;14.1.1 Understanding Stem Cell Biology for Therapeutic Applications;281
17.1.2;14.1.2 Fusogenicity as a Potential Property of Embryonic and Adult Stem Cells;282
17.2;14.2 Gamete Fusion;283
17.2.1;14.2.1 A Historic Perspective of Sperm-Egg Fusion;284
17.2.2;14.2.2 Gamete Cell Adhesion Is Facilitated by ADAM and Integrin Proteins;285
17.2.3;14.2.3 Tetraspanins as Oocyte Fusion Components;286
17.2.4;14.2.4 Sperm Membrane Fusion Proteins;287
17.2.5;14.2.5 Relevance of Gamete Fusion to Stem Cell Biology;287
17.3;14.3 Myoblast Fusion;288
17.3.1;14.3.1 A Brief History of Myoblast Fusion;289
17.3.2;14.3.2 Drosophila as a Model to Study Myoblast Fusion;289
17.3.3;14.3.3 Zebrafish as a Vertebrate Myoblast Fusion Model;290
17.3.4;14.3.4 Relevance of Myoblast Fusion Towards Understanding Other Stem Cell Fusion;290
17.4;14.4 Cell Fusion with Organ Stem Cells;291
17.4.1;14.4.1 Neural Stem Cell Fusion;291
17.4.2;14.4.2 Mesenchymal Stem Cell Fusion;293
17.4.3;14.4.3 Intestinal Stem Cell Fusion as a Regenerative Response to Injury;293
17.4.4;14.4.4 Relevance of Tissue Stem Cell Fusion to Tissue Physiology;297
17.5;14.5 Fusion of Hematopoietic Progenitors as a Source of Regenerative Repair;298
17.5.1;14.5.1 Evidence for Hematopoietic Fusion;298
17.5.2;14.5.2 Hematopoietic Regeneration of Liver Hepatocytes;299
17.5.3;14.5.3 Hematopoietic Regeneration of Heart Myocardium via Cell Fusion;300
17.6;14.6 Cancer Stem Cell Fusion;301
17.6.1;14.6.1 Cancer Stem Cell Hypothesis;301
17.6.2;14.6.2 Cell Fusion with Cancer Stem Cells;302
17.6.3;14.6.3 Genomic Instability in Cancer Stem Cell Fusion and Tumor Initiation;302
17.6.4;14.6.4 Fusion as a Mediator of Cancer Progression;303
17.7;14.7 Insight into the Physiologic Fate of Stem Cell Fusion;304
17.7.1;14.7.1 Nuclear Reprogramming Within Cell Fusion Hybrid Cells;304
17.7.2;14.7.2 Key Factors that Direct Nuclear Reprogramming;305
17.7.3;14.7.3 Directionality of Nuclear Reprogramming;306
17.7.4;14.7.4 Identification of Discrete Factors Important for Nuclear Reprogramming;307
17.7.5;14.7.5 Lessons from Stem Cell Fusion;307
17.8;14.8 Conclusion: The Biological Consequence for Stem Cell Fusigenicity;309
17.9;References;311
18;15 Cell Fusion and Dendritic Cell-Based Vaccines;317
18.1;15.1 Introduction;319
18.2;15.2 The Rationale for DC-Based Cell Fusion as Tumor Vaccine;320
18.3;15.3 Methods;323
18.3.1;15.3.1 Generation of DC from Murine Bone Marrow Cells;323
18.3.2;15.3.2 Preparation of Tumor Cells;325
18.3.3;15.3.3 Cell Fusion;325
18.4;15.4 Choice of Fusogen;326
18.4.1;15.4.1 PEG-Mediated Fusion;326
18.4.2;15.4.2 Electrofusion;327
18.4.3;15.4.3 Virus-Mediated Fusion;328
18.5;15.5 Selection of Fusion Cells;329
18.6;15.6 Modifications in Cell Fusion;330
18.6.1;15.6.1 Allogenic DC;330
18.6.2;15.6.2 Allogeneic Tumor Cells;331
18.6.3;15.6.3 Fusion Cells Expressing Cytokines;331
18.6.4;15.6.4 DC Maturation;332
18.7;15.7 Fusion Cell Vaccines and Antitumor Immunity;333
18.7.1;15.7.1 Animal Studies;334
18.7.2;15.7.2 Clinical Trials;338
18.8;15.8 Promotion of Antitumor Immunity;341
18.8.1;15.8.1 Using Adjuvant with Fusion Vaccine;341
18.8.2;15.8.2 Combined Approaches;342
18.9;15.9 Summary;343
18.10;References;344
19;16 Cancer Cell Fusion with Myeloid Cells: Implications for Energy Metabolism in Malignant Hybrids;353
19.1;16.1 Introduction;355
19.2;16.2 Cancer Cell Fusion In Vivo;357
19.3;16.3 Tumor Associated Macrophages as Candidates for Cancer Cell Fusion Partners;361
19.4;16.4 BMDCs in Human Cancer and Stem Cell-Like Distribution Patterns;365
19.5;16.5 Cancer Cell Fusion and the Hybrid Phenotype;367
19.6;16.6 Macrophage-Melanoma Fusion In Vitro Generates Altered Gene Expression and a Metastatic Phenotype In Vivo;367
19.6.1;16.6.1 SPARC;369
19.6.2;16.6.2 MCR1 and c-Met;370
19.6.3;16.6.3 GnT-V and 1,6-Branched Oligosaccharides;371
19.6.4;16.6.4 Motility-Associated Integrins;371
19.6.5;16.6.5 Cell Surface Expression of Lysosome Associated Protein-1 (LAMP-1);372
19.6.6;16.6.6 Autophagy and Coarse Melanin;372
19.6.7;16.6.7 Autophagy in Cutaneous Malignant Melanoma;373
19.7;16.7 Conclusions;385
19.8;16.8 Considerations for Studying Fusion In Vivo;385
19.9;16.9 Implications;386
19.10;References;387
20;17 Cell--Cell Fusions and Human Endogenous Retroviruses in Cancer;397
20.1;17.1 Development and Polyploidy;398
20.1.1;17.1.1 Short History of Cell--Cell Fusions;400
20.1.2;17.1.2 Cell--Cell Fusions in Development, Differentiation and Viral-Induced;401
20.1.2.1;17.1.2.1 Cytotrophoblasts-Syncytiotrophoblasts;402
20.1.2.2;17.1.2.2 Myoblasts-Myotubes;402
20.1.2.3;17.1.2.3 Osteoclasts;403
20.1.2.4;17.1.2.4 Unique Cell--Cell Fusions;403
20.1.2.5;17.1.2.5 Experimental Stem Cell Fusions;403
20.1.2.6;17.1.2.6 Virus Induced Cell Fusions;404
20.1.2.7;17.1.2.7 Bone Marrow Derived Cells (BMDC);404
20.1.3;17.1.3 Cell--Cell Fusions During Tumorigenesis;406
20.2;17.2 Human Endogenous Retroviruses (HERVs);410
20.2.1;17.2.1 HERV Expression in Human Cancers;414
20.2.2;17.2.2 HERVs in Cancer Cell--Cell Fusions: Driver or Passenger;415
20.3;17.3 CellCell Fusions in Cancer: Functional Role or Dead-End;416
20.4;References;419
21;Index;429