Molecular Biology Intelligence Unit

By: Paul Eggleton (Editor), Marek Michalak (Editor)

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Hardcover | 31 July 2003 | Edition Number 2

At a Glance

Hardcover
308 Pages

Edition Type
Revised

Dimensions(cm)
23.5 x 16.51 x 2.54

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The book focuses on the latest discoveries on calreticulin, calnexin and other endoplasmic reticulum proteins. Calreticulin has been implicated to affect diverse cellular function and play a role in many pathologies including protein folding disorders, cardiac pathologies, cancer and autoimmunity. This book contains contributions from the world leaders in the area of endoplasmic reticulum function, protein folding, Calcium homeostasis and autoimmunity. It raises many intriguing questions about calreticulin, calnexin and the endoplasmic reticulum and gives a unique opportunity to realize the significance of these calcium-binding chaperones. The book is unique in every respect and we are not aware of any other publication focusing on these aspects of endoplasmic reticulum biology. Because of a central role of endoplasmic reticulum, calreticulin and calnexin in virtually all cellular functions, the book should be of interest to everyone in the biological sciences.

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Non-Fiction Science Chemistry Organic Chemistry Medicine Pre-Clinical Medicine & Basic Sciences Physiology Metabolism Biology, Life Sciences Biochemistry Proteins

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Published: 1st November 2012

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Preface	p. xix
Abbreviations	p. xv
Introduction to Calreticulin	p. 1
Introduction	p. 1
Structure and Function of Calreticulin	p. 1
Protein Folding and Quality Control	p. 2
Ca[superscript 2+] Binding and Ca[superscript 2+] Homeostasis	p. 2
Immunological Functions of Calreticulin	p. 3
What Have We Learned from Calreticulin Gene Knockout?	p. 4
Calreticulin and Disease	p. 4
Calreticulin and Apoptosis	p. 5
Conclusions	p. 6
Biochemical and Molecular Properties of Calreticulin	p. 9
Abstract	p. 9
Introduction	p. 9
Domain Organisation of Calreticulin	p. 9
Glycosylation	p. 11
Disulphide Bridge	p. 11
Phosphorylation	p. 11
Recent Structural Studies on Calreticulin	p. 11
Structure of the P-Domain	p. 12
Structure/Function Relationships--Role of Cations	p. 12
Calreticulin Shows Sequence Homology to the Legume Lectins	p. 13
Model of Calreticulin--Implications of the Calnexin Structure	p. 15
Conclusions	p. 15
A Chaperone System for Glycoprotein Folding: The Calnexin/Calreticulin Cycle	p. 19
Abstract	p. 19
The ER As a Compartment for Protein Folding and Quality Control	p. 19
The Calnexin/Calreticulin Cycle	p. 20
The Structure of Calnexin and Calreticulin	p. 20
GT	p. 22
Glucosidase II	p. 23
ERp57	p. 23
ERp57 Binds the P-Domain of CRT	p. 24
Discussion	p. 24
Calnexin, an ER Integral Membrane Chaperone in Health and Disease	p. 30
Abstract	p. 30
Introduction	p. 30
The Structure of Calnexin	p. 31
Specific Interaction with ERp57	p. 34
Functions of Calnexin, Calreticulin and Calmegin	p. 34
Conclusions	p. 35
Sub-Cellular Distribution of Calreticulin	p. 38
Abstract	p. 38
Introduction	p. 38
Endoplasmic Reticulum	p. 39
Nucleus and Cytosol	p. 41
Cell Surface	p. 42
Extracellular	p. 43
Concluding Remarks	p. 45
Calnexin and Calreticulin, Molecular Chaperones of the Endoplasmic Reticulum	p. 49
Abstract	p. 49
Introduction	p. 49
Structure and Ligand Binding Properties of CNX and CRT	p. 50
Differences in Binding Specificity of CNX and CRT for Newly Synthesized Glycoproteins	p. 53
Molecular Chaperone Functions of CNX and CRT	p. 53
Mechanisms of Chaperone Action--The "Lectin Only" versus "Dual Binding" Controversy	p. 54
Concluding Remarks	p. 58
Roles of Calreticulin and Calnexin in Myeloperoxidase Synthesis	p. 63
Abstract	p. 63
Introduction	p. 63
Myeloperoxidase	p. 64
The Lectin Chaperones in the Biosynthesis of Normal MPO	p. 66
Quality Control in MPO Biosynthesis	p. 68
Summary	p. 71
Calreticulin-Mediated Nuclear Protein Export	p. 75
Abstract	p. 75
Nucleocytoplasmic Transport Pathways	p. 75
Purification of CRT Using an Export Assay	p. 76
Subcellular Distribution of CRT	p. 76
CRT Is the Export Receptor for GR	p. 77
Identification of the Export Signal in GR	p. 77
The DBD Is Necessary for Export	p. 79
Regulating GR Export	p. 81
Common Pathways for NR Transport	p. 81
Why Do Nuclear Receptors Undergo Export?	p. 82
Concluding Remarks	p. 83
The Role of Calnexin and Calreticulin in MHC Class I Assembly	p. 85
Abstract	p. 85
Introduction to Class I Assembly	p. 85
Functions of Calnexin in Class I Assembly	p. 86
Role of Calreticulin in Class I Assembly	p. 89
Concluding Remarks	p. 91
Calreticulin and the Endoplasmic Reticulum in Plant Cell Biology	p. 94
Abstract	p. 94
Introduction	p. 94
Characteristics of Plant Calreticulin	p. 94
Intracellular Localization of Calreticulin	p. 96
Inducible Expression of Calreticulin	p. 97
Endoplasmic Reticulum in Plant Cell Physiology	p. 99
Calreticulin and Ca[superscript 2+] Signalling	p. 101
Note Added in Proof	p. 101
Modulation of Calcium Homeostasis by the Endoplasmic Reticulum in Health and Disease	p. 105
Abstract	p. 105
Regulation of Endoplasmic Reticulum Ca[superscript 2+]	p. 105
The ER As Central Component of Compartmentalized Ca[superscript 2+] Signaling	p. 107
ER Calcium Homeostasis, Regulation of Cellular Proliferation and Apoptosis	p. 111
Diseases Associated with Ca[superscript 2+] Signaling Components of the ER	p. 114
Calnexin and Calreticulin, ER Associated Modulators of Calcium Transport in the ER	p. 126
Abstract	p. 126
Introduction	p. 126
Xenopus Oocytes As an Expression System	p. 127
Calreticulin and Calnexin Have an Inhibitory Effect on Ca[superscript 2+] Oscillations	p. 127
Inhibition of Ca[superscript 2+] Oscillations Is Mediated by the COOH Terminus of SERCA2b	p. 128
Interaction of CNX with the COOH Terminus of SERCA2b	p. 129
A PKC Phosphorylation Site in CNX Regulates Inhibition of Ca[superscript 2+] Oscillations	p. 129
ER Calcium and ER Chaperones: New Players in Apoptosis?	p. 133
Abstract	p. 133
Introduction	p. 133
Role of ER Calcium in Apoptosis	p. 134
Role of ER Chaperones in Apoptosis	p. 136
Calreticulin in Cytotoxic Lymphocyte-Mediated Cytotoxicity	p. 142
Abstract	p. 142
Introduction	p. 142
Cytotoxic Lymphocytes and the Contents of the Granules	p. 143
The Role of Calreticulin in Perforin-Dependent Lysis	p. 145
Other Functions for Calreticulin in Immunity	p. 148
Conclusions	p. 148
A Role for Calreticulin in the Clearance of Apoptotic Cells and in the Innate Immune System	p. 151
Abstract	p. 151
Introduction	p. 151
The Collectin Family of Pattern Recognition, Innate Immune System, Molecules	p. 153
Collectin Interaction with Cell Surface Calreticulin	p. 154
Interaction of Calreticulin with CD91/LRP As a Mechanism for Initiating Apoptotic Cell Internalization	p. 155
Mechanisms of Uptake and Signaling	p. 157
Conclusions	p. 158
Calreticulin and Tumor Suppression	p. 162
Abstract	p. 162
Introduction	p. 162
Isolation of Calreticulin NH[subscript 2] Terminal Fragments and Calreticulin and Their Identification As Inhibitors of Endothelial Cells Proliferation	p. 163
Effects of Calreticulin and Calreticulin Fragments on Endothelial Cell Proliferation	p. 165
Effects of Calreticulin on Endothelial Cell Attachment	p. 167
Calreticulin and Calreticulin N-Domain Inhibit Angiogenesis	p. 170
Anti-Tumor Effects of Calreticulin and Calreticulin N-Domain	p. 171
Concluding Remarks	p. 177
Calreticulin's Role(s) in Autoimmune Disorders	p. 180
Abstract	p. 180
Introduction	p. 180
Cellular Localization of CRT	p. 180
Immune Related Functions of CRT	p. 181
CRT As Autoantigen	p. 183
How Does CRT Become Accessible to the Adaptive Immune System?	p. 185
Why CRT Might Be Targeted As Nonself	p. 185
Can the CRT Autoimmune Response Be Viewed As a Heat Shock Response?	p. 186
Observed Immunochemical Characteristics of the CRT Aab Response	p. 186
CRT Specific Cell Mediated Immune Responses	p. 187
Pathogenetic Significance of the CRT Autoimmune Response	p. 188
Final Thoughts on the Role of CRT in Autoimmune Disease	p. 188
Cell Surface Calreticulin: Role in Signaling Thrombospondin Anti-Adhesive Activity	p. 193
Abstract	p. 193
Introduction--Calreticulin: A Ubiquitous Protein with Diverse Functions	p. 193
Calreticulin Is a Cell Surface Protein	p. 194
TSP-Mediated Focal Adhesion Disassembly	p. 194
Cell Adhesion and De-adhesion	p. 195
Cell Surface CRT As a Receptor for TSP-Mediated Focal Adhesion Disassembly	p. 196
Signaling of CRT/TSP Focal Adhesion Disassembly	p. 199
Physiologic Significance of Cell Surface Calreticulin	p. 199
Summary and Significance	p. 201
Calreticulin Regulation of Lung Endothelial NOS Activity	p. 205
Abstract	p. 205
Introduction	p. 205
Biochemistry and Physiology of Ang-IV	p. 206
Calreticulin Expression and Function: Role of Cell Stimulation/Injury	p. 207
Structure, Function, and Regulation of eNOS Activity	p. 208
Ang-IV eNOS Activation: Link to Cellular Calcium and Calreticulin	p. 209
Concluding Remarks	p. 216
Role of Calreticulin in Leishmania Parasite Secretory Pathway and Pathogenesis	p. 220
Abstract	p. 220
Leishmania Biology	p. 220
Secretory Pathway in Trypanosomatids	p. 222
Characterization of ER Chaperones in Trypanosomatids	p. 223
Role of Calreticulin in Leishmania Secretory Pathway	p. 225
Dominant-Negative Effect of Expression of Putative Domains of LdCR on the Parasite Survival in Macrophages in Vitro	p. 231
Conclusion	p. 234
The Hookworm Calreticulin Conundrum	p. 238
Abstract	p. 238
Introduction	p. 238
Hookworm Calreticulin May Be Secreted to Perform Important Biological Functions at the Host Parasite Interface	p. 238
Affinity Purification of Native N. americanus Calreticulin	p. 239
The True Allergenicity of Hookworm Calreticulin?	p. 240
Antigenicity of Hookworm Calreticulin	p. 240
The Way Forward	p. 246
Summary	p. 247
Calreticulin in C. elegans	p. 248
Abstract	p. 248
Introduction	p. 248
Caenorhabditis elegans As a Model Organism	p. 248
crt-1 Gene and Protein	p. 249
In vitro Function	p. 249
The Isolation of C. elegans crt-1 Mutants	p. 249
In vivo Functions of Calreticulin	p. 249
ER-Mediated Calcium Homeostasis and Cell Death	p. 251
Defecation Cycle	p. 252
crt-1 Is Not Essential for Receptor-Mediated Endocytosis	p. 252
Future Prospective	p. 252
An Evolutionary View of the Functions of Calreticulin	p. 253
Calreticulin Deficient Mouse	p. 258
The Calreticulin Gene Knockout Mouse	p. 258
Cranial Neural Tube Closure and Umbilical Hernia in Calreticulin-Deficient Embryos	p. 258
Cardiac Pathology in Calreticulin-Deficient Embryos	p. 260
How Does Calreticulin-Deficiency Result in Impaired Cardiac Development?	p. 261
The Calreticulin-Deficient Mouse Shows that Cardiac ER and SR Compartments Are Functionally Distinct	p. 262
The Effects of Calreticulin Over-Expression in Postnatal Heart and Its Role in Congenital Complete Heart Block	p. 262
Conclusions	p. 263
Human Calreticulin Data Sheet	p. 267
Previous Names	p. 267
Physicochemical Properties	p. 267
Mature Protein	p. 267
N-Linked Glycosylation Sites (Species Specific)	p. 267
Interchain Disulphide Bonds	p. 267
Phosphorylation	p. 268
Ion-Binding Characteristics	p. 268
Gene Structure	p. 268
Commercial Antibodies Raised against Calreticulin	p. 268
Amino Acid Sequence of Calreticulin	p. 271
Index	p. 279
Table of Contents provided by Rittenhouse. All Rights Reserved.

Molecular Biology Intelligence Unit

At a Glance

Hardcover

Shipping

How to return your order

Defective items

You Can Find This Book In

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Paperback

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