Cover 1
Copyright Page 5
Contents 6
Contributors 8
Chapter 1: Mechanisms of Gradient Detection: A.Comparison of Axon Pathfinding with Eukaryotic Cell Migration 10
1. Introduction 11
2. Mechanisms of Gradient Detection in Selected Eukaryotic Cell Types 13
2.1. Chemotaxis of Dictyostelium 13
2.2. Chemotaxis of mammalian neutrophils 19
2.3. Chemotaxis of mammalian fibroblasts 23
2.4. Pathfinding of neuronal growth cones 28
3. Common Grounds and Diversity 50
3.1. Signaling pathways 50
3.2. Signal amplification 56
3.3. Adjustment of sensitivity/adaptation 58
3.4. Biological and functional context 59
4. Concluding Remarks 60
Acknowledgments 61
References 61
Chapter 2: Leptin and the Regulation of the Hypothalamic-Pituitary-Adrenal Axis 72
1. Introduction 73
2. Biology of Leptin and Its Receptors 74
2.1. Leptin 74
2.2. Leptin receptors 77
3. Expression of Leptin and Its Receptors in the Hypothalamic-Pituitary-Adrenal Axis 78
3.1. Hypothalamus 78
3.2. Anterior pituitary 79
3.3. Adrenal gland 82
4. Effects of Leptin on the Central Branch of the Hypothalamic-Pituitary-Adrenal Axis 85
4.1. Hypothalamus and CRH secretion 85
4.2. Anterior pituitary and ACTH secretion 86
5. Effects of Leptin on the Peripheral Branch of the Hypothalamic-Pituitary-Adrenal Axis 87
5.1. Adrenal cortex 87
5.2. Other steroid-secreting cells 92
5.3. Adrenal medulla 93
6. Involvement of Leptin in the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis 94
6.1. Response to stresses 94
6.2. Pituitary adenomas 95
6.3. Adrenocortical tumors and pheochromocytomas 95
6.4. Macronodular adrenal hyperplasia 96
6.5. Hyperreninemic hypoaldosteronism 96
7. Concluding Remarks 97
Acknowledgments 98
References 98
Chapter 3: Focal Adhesion Kinase and p53 Signaling in Cancer Cells 112
1. Introduction 113
2. Structure and Function of Focal Adhesion Kinase Protein 114
2.1. FAK structure 114
2.2. FAK functioning in cells 120
2.3. FAK-protein binding partners 123
3. FAK in Tumorigenesis 131
3.1. Overexpression in tumors 131
3.2. FAK and stem cells 137
4. FAK and p53 Association 138
4.1. Structure and function of the p53 protein 139
4.2. p53 mutations in cancer cells 141
4.3. p53 binds the FAK promoter 141
4.4. Direct FAK and p53 protein binding 142
4.5. Cytoplasmic-nuclear protein shuttling 142
4.6. Feedback model of FAK-p53 protein interaction 143
5. FAK and p53 Targeted Therapy 145
5.1. Downregulation of FAK 145
5.2. FAK inhibitors 145
5.3. Targeting protein-protein interactions 146
5.4. p53 therapy 146
6. Summary 147
Acknowledgments 147
References 147
Chapter 4: Cell and Molecular Biology of the Spindle Matrix 164
1. Introduction 165
2. Microtubule Spindle Dynamics and Force Production 166
3. Evidence for a Spindle Matrix 170
3.1. Early indications of abundant nonmicrotubule components of the spindle and spindle remnants 172
3.2. Chromosome movement after UV microbeam severing of microtubules 173
3.3. Molecular identification of a multiprotein spindle matrix complex in Drosophila 174
3.4. Spindle length and the spindle matrix 182
3.5. Membranes and the spindle matrix 183
3.6. Other molecular candidates for an internal spindle matrix structural element 184
3.7. Spindle assembly factors (SAFs) and the spindle matrix 193
4. Concluding Remarks 197
Acknowledgments 199
References 199
Chapter 5: Mitochondrial Biology and Disease in Dictyostelium 216
1. Introduction 217
2. Mitochondrial Biology 218
2.1. Mitochondrial genetics 218
2.2. Protein import into mitochondria 224
2.3. Mitochondrial morphology and division 226
2.4. Mitochondria and programmed cell death in Dictyostelium 230
3. Mitochondrial Disease 232
3.1. Mitochondrial disease in humans 232
3.2. Genetic methods for creating mitochondrial disease in Dictyostelium 234
3.3. Mitochondrial disease phenotypes and associated signaling pathways 238
3.4. Phenotypic thresholds in mitochondrial disease in Dictyostelium 244
3.5. Phenotypes associated with mitochondrial defects not known to affect respiration 245
3.6. AMPK-the missing link between phenotype and genotype in mitochondrial disease 247
3.7. Implications 250
4. Concluding Remarks 251
References 252
Chapter 6: Oxytocin and the Human Prostate in Health and Disease 262
1. Introduction 263
2. The Human Prostate 263
2.1. Structure 263
2.2. Functions 266
3. Oxytocin and Oxytocin Receptor 268
3.1. Regulation and structure 269
3.2. Signaling pathways used by the oxytocin receptor 271
4. Oxytocin and the Prostate 273
4.1. Overview of oxytocin and neurophysin in the male reproductive tract 273
4.2. Local production of oxytocin and neurophysin in the prostate 276
4.3. Functions of oxytocin in the prostate 279
4.4. Oxytocin and prostate disease 281
5. Possible Roles of Oxytocin in the Pathophysiology of Prostate Disease 283
5.1. Benign prostatic hyperplasia 284
5.2. Carcinoma of the prostate 284
5.3. Problems with animal models of human prostate disease 285
5.4. Possible therapeutic roles for oxytocin 286
6. Concluding Remarks 287
References 287
Index 296