Cellular Peptide Hormone Synthesis and Secretory Pathways

1. Auflage 2010
ISBN: 978-3-642-11836-4
Verlag: Springer
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 239 Seiten

The concept of hormonal regulation using intercellular peptide messengers dates back to the discovery of secretin in 1902. The concept was simple: A peptide is released from specific hormone producing cells, endocrine cells, into circulation upon stimulation of the cells. The peptide hormone travels via blood to its target, the cells of which are equipped with specific receptors for high-affinity binding of the particular peptide hormone. Receptor binding subsequently elicits action of the target cells. This concept has been seriously challenged by modern biochemistry and cell biology. Thus, it is now well established that the gene of a specific peptide hormone may be expressed in different types of endocrine cells, in neurons, and in some instances also in adipocytes, myocytes, osteoblasts, and immune cells. Today, only a few hormones – including the old master hormone insulin – represent the original endocrine paradigm. Instead, the widespread cellular synthesis now raises the qu- tion of how the body maintains the regulation of its functions by peptide hormones when a hormone may originate from a variety of cells.

Autoren/Hrsg.

Inhaltsverzeichnis

1;Preface;5
2;Maturation of Secretory Granules;9
2.1;1 Introduction;9
2.2;2 Formation of ISGs at the TGN;11
2.2.1;2.1 Aggregation;11
2.2.2;2.2 Sorting Motifs and Cargo–Membrane Interaction;12
2.3;3 Transport of Maturing ISGs;14
2.4;4 Mechanistic Insights into ISG Maturation;15
2.4.1;4.1 Homotypic Fusion;16
2.4.2;4.2 Sorting by Retention;16
2.4.3;4.3 Acidification;18
2.5;5 Maturation into Vesicle Pools ;19
2.6;6 Summary;22
2.7;References;22
3;Chromogranins A and B and Secretogranin II as Prohormones for Regulatory Peptides from the Diffuse Neuroendocrine System;29
3.1;1 Introduction;29
3.2;2 Granins and Granin-Derived Peptides;30
3.2.1;2.1 The Prohormone Concept;30
3.2.2;2.2 CgA;31
3.2.3;2.3 CgB;32
3.2.4;2.4 SgII;33
3.3;3 Functional Aspects ;33
3.4;4 Granin Peptides and Targets;36
3.4.1;4.1 Antimicrobial Potencies and Innate Immunity;36
3.4.2;4.2 Inflammatory Conditions;37
3.4.3;4.3 Other Cardiovascular Functions;40
3.4.4;4.4 CgA Peptides as Modulators of Calcium and Carbohydrate Homeostasis;43
3.5;5 Towards a Unifying Concept for Extracellular Functions of CgA, CgB, and SgII;44
3.6;References;46
4;Cell-Specific Precursor Processing;53
4.1;1 Introduction;53
4.2;2 Examples of Cell-Specific Prohormone Processing ;55
4.3;3 Significance of the Cell-Specific Processing in Disease;62
4.4;4 Processing-Independent Analysis;64
4.5;5 Summary;65
4.6;References;66
5;ACTH: Cellular Peptide Hormone Synthesis and Secretory Pathways;71
5.1;1 Introduction;71
5.2;2 POMC Synthesis and Its Regulation;73
5.3;3 POMC Processing: The Peptides Produced and the Cleavage Pathway;74
5.3.1;3.1 Processing of POMC to ACTH;74
5.3.2;3.2 Processing of ACTH by PC2;75
5.3.3;3.3 Post-Translational Processing to Produce aMSH;75
5.4;4 The Secretion of Processed POMC Peptides ;76
5.5;5 Incomplete Processing of POMC: When, How and Why?;84
5.6;6 Conclusion;87
5.7;References;88
6;Neurotensin and Neuromedin N Are Differentially Processed from a Common Precursor by Prohormone Convertases in Tissues and Cell Lines;93
6.1;1 Introduction;93
6.2;2 The Neurotensin Precursor Also Contains Neuromedin N;95
6.3;3 Pro-NT/NN Is Differentially Processed in Tissues and Cell Lines;95
6.3.1;3.1 Differential Processing in the Brain, Gut and Adrenals;96
6.3.2;3.2 Processing in Cell Lines;96
6.4;4 Pro-NT/NN Processing by Prohormone Convertases;98
6.5;5 Involvement of PCs in Pro-NT/NN Processing in Tissues and Cell Lines ;99
6.6;6 Carboxypeptidase E and Dibasic Removal;100
6.7;7 Physio-Pathological Implications;101
6.8;8 Conclusions;102
6.9;References;102
7;Biosynthesis of Cardiac Natriuretic Peptides;105
7.1;1 Introduction;105
7.2;2 Peptide Nomenclature and Biosynthesis;107
7.3;3 The Pre-Translational Phase of B-Type Natriuretic Peptide Gene Expression;108
7.4;4 The Primary Structure of ProBNP;110
7.5;5 The Post-Translational Phase of B-Type Natriuretic Peptide Gene Expression;111
7.5.1;5.1 Disulphide Bond Formation;111
7.5.2;5.2 Glycosylation;112
7.5.3;5.3 Endoproteolysis;114
7.5.4;5.4 Exoproteolysis;115
7.6;6 Cellular Storage and Secretion;116
7.7;7 ProBNP-Derived Peptides in Plasma;118
7.8;8 Biosynthesis and Assay Calibration;119
7.9;9 Inefficient Prohormone Maturation in Heart Failure;120
7.10;10 Concluding Remarks;121
7.11;References;122
8;Glucagon and Glucagon-Like Peptides 1 and 2;129
8.1;1 Introduction;129
8.2;2 Proglucagon Gene Expression;132
8.3;3 Posttranslational Processing and Chemical Structures;134
8.4;4 Localization of Proglucagon Expression;136
8.5;5 Postsecretory Fate of Proglucagon-Derived Peptides;137
8.6;References;139
9;Somatostatin and Somatostatin Receptors;144
9.1;1 Introduction;144
9.2;2 Somatostatin Processing;146
9.3;3 Somatostatin Distribution;147
9.4;4 Somatostatin Physiology;148
9.5;5 Somatostatin Regulation;150
9.6;6 A New Member in the Somatostatin Family?;151
9.7;7 Somatostatin Receptors;152
9.8;8 Development of Somatostatin Receptor Ligands;154
9.9;9 Somatostatin Receptor Localization;156
9.10;10 Regulation of Somatostatin Receptor Genes;158
9.11;11 Somatostatin Receptor Signaling;158
9.12;12 Relevance of SSTRs in Cancer;161
9.13;13 Agonist-Regulation of Somatostatin Receptors;164
9.14;14 Dimerization of SSTRs;168
9.15;15 Conclusions;172
9.16;References;173
10;Ghrelin: From Gene to Physiological Function;192
10.1;1 Introduction;192
10.2;2 Genomic Structure of Ghrelin;193
10.3;3 Promoter and Expression of Ghrelin Gene;195
10.4;4 Processing of Ghrelin Precursor to Des-Acyl Ghrelin;195
10.5;5 Acyl-Modification of Ghrelin by Ghrelin O- Acyltransferase ( GOAT);197
10.6;6 Substrate Specificity of GOAT;198
10.7;7 n-Octanoyl Ghrelin Is the Major Form of Gastric Ghrelin;199
10.8;8 Des-Acyl Ghrelin;199
10.9;9 Multiple Forms of Ghrelin in Human Stomach;200
10.10;10 Molecular Forms of Ghrelin in Jejunum, Pancreas and Hypothalamus;200
10.11;11 Obestatin, a Ghrelin Precursor-Derived Peptide?;200
10.12;12 Regulation of Ghrelin Secretion;201
10.13;13 Abnormal Ghrelin Secretion in Prader–Willi Syndrome;203
10.14;14 Pathway of Ghrelin Signal: From Peripheral Tissues to Central Nervous System;203
10.15;15 Ghrelin Stimulates Appetite in the Hypothalamus;204
10.16;16 Molecular Mechanism of Appetite Stimulation by Ghrelin;206
10.17;17 Epilogue;207
10.18;References;208
11;Posttranslational Processing of Progastrin;213
11.1;1 Introduction;214
11.2;2 The Structure of Progastrin;215
11.3;3 Intracellular Transport and Posttranslational Processing Events;216
11.4;4 Processing Characteristics of Progastrin;218
11.5;5 A Model for the Biosynthesis of Progastrin;222
11.6;6 Conclusions;223
11.7;References;223
12;VIP and PACAP;227
12.1;1 Introduction;227
12.2;2 Discovery of VIP;228
12.3;3 Structure of the VIP Precursor;228
12.4;4 Co-Existence and Co-Secretion of VIP and PHI;229
12.5;5 Glycine-Extended VIP;230
12.6;6 Expression of Other VIP Precursor-Derived Peptides;231
12.7;7 PreproVIP-Derived Peptides in Patients with VIP- Producing Tumours;233
12.8;8 Discovery of PACAP;233
12.9;9 Structure of PACAP Precursor;234
12.10;10 Expression of PACAP Precursor-Derived Peptides;235
12.11;11 Conclusion;237
12.12;References;237
13;Index;241