G Protein-Coupled Receptors in Health and Disease, Part A (eBook)

Ya-Xiong Tao (Herausgeber)

eBook Download: PDF

2009 | 1. Auflage
224 Seiten
Elsevier Science (Verlag)
978-0-08-091195-3 (ISBN)

Infos

G protein-coupled receptors (GPCRs) transduce signals from a diverse array of endogenous ligands, including ions, amino acids, nucleotides, lipids, peptides, and large glycoprotein hormones. They are also responsible for our sensing of exogenous stimuli, including photons and odorants. GPCRs regulate almost every aspect of our physiological functions. It is estimated that 40% to 50% of currently used therapeutic drugs target GPCRs directly or indirectly. Because the current drugs target only a small portion of the GPCRs, opportunities for targeting the remaining GPCRs is enormous. This volume reviews the latest developments in this rapidly advancing field.

* This series provides a forum for discussion of new discoveries, approaches, and ideas * Contributions from leading scholars and industry experts * Reference guide for researchers involved in molecular biology and related fields

Inhalt

Front Cover 1
Progress in Molecular Biology and Translational Science 4
Copyright Page 5
Contents 6
Contributors 10
Preface 12
Chapter 1: Rhodopsin-Mediated Retinitis Pigmentosa 14
I. Introduction 15
II. Rhodopsin Function 16
A. Retina Structure 16
B. Rod Cell-Specific Expression of Rhodopsin 18
C. Classification of Rhodopsin Mutations 20
III. Mechanisms of Rod Degeneration 22
A. P23H, VPP: A Model for Misfolded and Mislocalized Rhodopsin Mutants 22
B. P347S: A Model for a Nonautonomous Pathway and Destabilized Rhodopsin Mutants 25
C. K296E: A Model for Persistent Signaling and Alternative Signaling Pathways 29
IV. Mechanisms of Cone Degeneration 31
A. Trophic Factors 31
B. Toxic Factors 33
C. Metabolic Support 34
V. Treatments 35
A. Gene Therapy 35
B. Vitamin A and Pharmacological Supplementation 38
C. Transplantation of Stem Cells or Retinal Sheets 39
VI. Conclusions 40
References 41
Chapter 2: Human Diseases Associated with GPR54 Mutations 46
I. Introduction 47
II. Structure and Expression of GPR54 48
III. The GPR54 Ligand 50
IV. GPR54 and KISS1 Genes in Evolution 51
V. Kisspeptin/GPR54 Signaling Pathway 52
VI. KISS1/GPR54 and Cancer 53
VII. Neuroendocrine Studies 54
VIII. Expression Studies 56
IX. gpr54 and kiss1 Knockout Mice 57
X. Loss-of-Function Mutations of GPR54 57
XI. The Role of GPR54 in Central Precocious Puberty 62
XII. Conclusion 64
References 64
Chapter 3: Diseases Associated with Growth Hormone-Releasing Hormone Receptor (GHRHR) Mutations 70
I. Introduction 71
II. GHRHR Biology 73
A. GHRHR and Its Ligand 73
B. Signal Transduction 74
C. GHRHR Structure 75
D. GHRHR Organization and Regulation 77
E. GHRHR Splice Variants 78
III. GHRHR Mutations and Polymorphisms 79
A. GHRHR Mutations 79
B. GHRHR Polymorphisms 83
IV. Diseases Associated with GHRHR Mutations 83
A. Clinical Characteristics of Homozygous Individuals 83
B. Clinical Characteristics of Heterozygous Carriers 86
V. Conclusions 87
References 88
Chapter 4: The Melanocortin-1 Receptor Gene Polymorphism and Association with Human Skin Cancer 98
I. Introduction 99
II. Human Pigmentation and Skin Phototypes 100
A. The Melanocyte 100
B. Melanin 102
C. Melanosome Maturation 102
D. Melanogenic Enzymes and Pigmentation Genes 104
E. UVR-Induced DNA Damage 109
III. The Discovery of MC1R and Its Role in the Regulation of Pigmentation 110
A. Tanning 111
B. MC1R-Mediated cAMP Signaling 111
C. Pheomelanin to Eumelanin ``Switch´´ 112
D. Alternative MC1R Signaling Pathways 112
E. Calcium Signaling 113
F. MAPK/ERK Pathway 114
G. Agouti Signaling Protein 114
H. beta-Defensin 3 115
IV. MC1R and the Red Hair Phenotype 116
A. MC1R Gene Evolution and Population Allele Frequencies 116
V. MC1R Variant Allele Function 117
A. Intracellularly Retained 123
B. Pseudo-Wild Type 123
C. G-Protein Coupling Defective 123
D. Altered Ligand Binding 123
E. Altered Internalization 124
F. Null Alleles 124
G. MC1R Variant Function in Coculture 124
H. Comparison of SNPs in the Melanocortin Receptor Family 124
VI. MC1R Structure, Activity, and Regulation 127
A. MC1R Motifs 128
VII. MC1R and Skin Cancer Risk 134
1. Is the Association with Skin Cancer Solely Explained by Pigmentation Phenotype? 137
A. MC1R and DNA Repair 138
B. MC1R and CDKN2A Familial Melanoma 138
C. MC1R and BRAF Mutant Melanoma 138
D. MC1R, Freckling, and Nevi 139
E. MC1R and Melanocytic Morphology 140
VIII. MC1R and Nonpigmentary Functions 140
A. MC1R and Inflammation 140
B. MC1R and Pain Sensitivity 141
C. MC1R and Multiple Sclerosis 141
D. MC1R and Vitiligo 141
IX. Therapeutic Applications of MC1R Research 141
References 144
Chapter 5: The Molecular Basis of Adrenocorticotrophin Resistance Syndrome 168
I. Introduction 169
II. Melanocortin-2 Receptor 169
III. Melanocortin-2 Receptor Accessory Protein 171
IV. Familial Glucocorticoid Deficiency 171
A. Clinical Features 171
V. Etiology of Familial Glucocorticoid Deficiency 173
VI. Triple A Syndrome 174
A. Clinical Features 174
VII. Etiology of Triple A Syndrome 177
VIII. Concluding Remarks 178
References 178
Chapter 6: Mutations in Melanocortin-4 Receptor and Human Obesity 186
I. Introduction 186
II. The Melanocortin System 187
III. The Leptin-Regulated Melanocortin Circuit 188
IV. Melanocortin-4 Receptor and Energy Homeostasis 191
V. Naturally Occurring Mutations in MC4R Gene and Human Obesity 192
A. Identification of MC4R Mutations 192
B. Prevalence of MC4R Mutations 194
C. Clinical Phenotypes of Patients Harboring MC4R Mutations 195
D. Functional Characterizations of the MC4R Mutants 197
E. Molecular Classification of the MC4R Mutants 199
F. Insights into the Structure and Function of the MC4R 202
VI. Potential Therapeutic Strategies 204
VII. Conclusions 205
References 207
Index 218
Color Plate 226

Produkt-Details

• Erscheint lt. Verlag: 5.8.2009
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Studium ► Querschnittsbereiche ► Prävention / Gesundheitsförderung
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Technik
• ISBN-10: 0-08-091195-1 / 0080911951
• ISBN-13: 978-0-08-091195-3 / 9780080911953