Wnt Signaling in Development and Disease E-Book

Stefan P. Hoppler

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1406

Veröffentlichungsjahr: 2014

Beschreibung

Wnt signaling in Development and Disease: Molecular Mechanisms and Biological Functions reviews the core topics in Wnt signaling, from molecular pathway mechanisms to its role in embryogenesis, adult tissue homeostasis, and chronic disease. Written by a team of expert reviewers, the book provides clear and concise coverage of the core foundations of Wnt signaling before advancing to discussion of cutting-edge scientific research. Focused on the biological insights and current scientific questions of Wnt signaling, this book will be a comprehensive and definitive resource for a wide range of researchers and students in cell signaling, cell physiology, developmental biology, and biomedical engineering, as well as anyone interested in learning more about this important and complex protein network. * A definitive source of information on Wnt signaling and its role in development and disease, written by leaders in the field. * Explores the role of Wnt signaling in chronic disease such as melanoma, colorectal cancer, dementia, and psychiatric diseases * Reviews the complex processes of signal integration and regulation * Features broad discussion of Wnt signaling biology as well as detailed discussion of the pathway's role in diseases and potential clinical applications.

Leseprobe

CONTENTS

Cover

Title page

Copyright page

Contributors

Preface

Part 1: Molecular Signaling Mechanisms

1 Wnt Signal Production, Secretion, and Diffusion

Introduction

Posttranslational modification of Wnt

The Wnt secretion pathway

Mechanisms that promote and control the diffusion of Wnt

Conclusions and perspectives

References

2 Wnt Signaling at the Membrane

Introduction

The Frizzled family of Wnt receptors

The LRP family of Wnt coreceptors

Acknowledgments

References

3 Wnt Signal Transduction in the Cytoplasm:

Introduction: A central role for control of β-catenin degradation in the Wnt pathway

Components of the β-catenin destruction complex

Formation of the β-catenin destruction complex

β-Catenin degradation by the destruction complex

Models for inhibition of β-catenin degradation

β-Catenin turnover as a futile cycle

Acknowledgments

References

4 An Overview of Gene Regulation by Wnt/β-Catenin Signaling

Introduction

TCFs and transcriptional switches

Coregulators of β-catenin/TCF transcription

Other TFs that mediate Wnt/β-catenin signaling

Concluding comments

Acknowledgments

References

5 Finding a Needle in a Genomic Haystack:

TCFs: Major nuclear mediators of Wnt/β-catenin signaling

Identification of Wnt target genes

Genome-wide studies of TCF binding

Conclusions

Acknowledgments

References

6 Introduction to β-Catenin-Independent Wnt Signaling Pathways

Introduction

Wnt/calcium signaling

Planar cell polarity signaling

Cilia formation and function: Components of PCP signaling

Wnt/rho/ROCK and Wnt/rac/JNK signaling

Wnt/Ror signaling

Wnt/Ryk signaling

Wnt/cAMP/protein kinase A

Wnt/TOR signaling

Outlook

References

7 Molecular Mechanismsof Wnt Pathway Specificity

Early Wnt classifications

Wnt5a exemplifies the ability of Wnts to activate multiple signaling cascades

Multiple signaling routes through single Frizzled family members

Determinants of Wnt pathway specificity

Perspectives

Acknowledgments

References

8 Modulation of Wnt Signaling by Endocytosis of Receptor Complexes

Introduction

Endocytic pathways

Selective activation of Wnt signaling pathways by receptor-mediated endocytosis

Regulation of Wnt signaling by receptor ubiquitination

Concluding remarks and future perspectives

Acknowledgments

References

9 New Insights from Proteomic Analysis of Wnt Signaling

A brief introduction to protein mass spectrometry

Protein–protein interaction networks and activity-based proteomics

Quantitative proteomics

Network analysis of β-catenin-dependent WNT signaling

Integration of previously described APMS experiments

Proteomic discovery of WNT pathway biomarkers

Conclusion

Acknowledgments

References

10 New Insights about Wnt/β-Catenin Pathway Mechanisms from Global siRNA Screens

Understanding cell signaling pathways in the postgenomic era

The Wnt/Wg signaling pathway

Cross-regulatory interactions between Wnt and other signaling pathways

RNAi-based whole-genome screens for modulators of the Wnt/wg pathway

Context-dependent modulation of the Wnt/β-cat signaling pathway

Functionally targeted RNAi screens

Querying the cancer genome

Integration of RNAi screens with genomic and proteomic approaches

Conclusion

References

11 Mathematical Modelsof Wnt Signaling Pathways

Introduction

Modeling approaches in signal transduction

Wnt/β-catenin signaling: Lessons learned from mathematical models

PCP signaling: Insights gained from mathematical models

Future challenges

References

12 The Wnt’s Tale

Introduction

Conclusions and outlook

Acknowledgments

References

Part 2: Selected Key Molecules in Wnt Signaling

13 Secreted Wnt Inhibitors or Modulators

Introduction

Modulators that interact with Wnt proteins

Modulators that interact with Wnt pathway components

Pathological implications of Wnt modulators’ malfunction

Conclusions

References

14 Frizzleds as G Protein-Coupled Receptors

Introduction

Frizzled structure and molecular pharmacology

Frizzled dimerization

Activating ligand of Frizzleds

Ligand-receptor selectivity and possibilities for ligand trafficking

Doubtful liaison (or just a bit different?): FZDs and heterotrimeric G proteins

FZD–G protein signaling

Biological relevance of WNT-induced G protein signaling

Conclusions and future challenges

Acknowledgments

References

15 Dishevelled at the Crossroads of Pathways

Introduction

Structure of Dvl

Dvl-associated kinases and consequences of Dvl phosphorylation

Dvl stability and ubiquitination

Dvl in the Wnt/β-catenin and Wnt/PCP pathway: What makes a difference?

Remaining secrets of Dvl

References

16 β-Catenin

Introduction

Cell adhesion function of β-catenin

Wnt signaling function of β-catenin

Relating structure to function

Choosing where to go and what to do

Subfunctionalization of β-catenins

Perspective

References

17 Evolutionary Diversification of Vertebrate TCF/LEF Structure, Function, and Regulation

Genome duplications enrich the vertebrate complement of Wnt signaling components

Shared features of invertebrate and vertebrate TCF structure and function

Novel and specialized TCF structures and functions created by differential transcriptional regulation

Novel and specialized TCF proteins from altered and alternative splicing

Conclusions

References

18 Insights from Structural Analysis of Protein–Protein Interactions by Wnt Pathway Components and Functional Multiprotein Complex Formation

Structure of Wnt and a Wnt–Frizzled complex

Structures of LRP5/6 and LRP6-containing complexes

Other complexes regulating the formation of the Fzd–Wnt–LRP signaling complex: WIF1, sFRP, and the LGR–RSPO complexes

Interactions of Axin and Dishevelled with the cytoplasmic side of Wnt receptor and coreceptors

Structural basis of β-catenin turnover and the β-catenin destruction complex

Nuclear protein complexes crucial for Wnt signaling

References

Part 3: Wnt Signaling in Embryonic Development and Adult Tissue Homeostasis

19 Wnt Signaling in Early Vertebrate Development:

Introduction

Induction of embryonic axis by maternal Wnt/β-catenin signaling

Axial patterning of the mesoderm through zygotic Wnt/β-catenin signaling

Wnt/β-catenin signaling in early mammalian development

Wnt signaling in the control of morphogenesis

Relationship between Wnt signaling and core planar cell polarity (PCP) proteins

Conclusions

References

20 Wnt/β-Catenin Signaling in Embryonic Stem Cells

Introduction to pluripotent stem cells

Naïve versus prime state pluripotency

Wnt/β-catenin signaling in embryonic stem cells

Wnt/β-catenin signaling promotes acquisition of pluripotency

A core pluripotency transcriptional network

Summary

Acknowledgments

References

21 Wnt Signaling in Neural Development

Introduction

CNS induction and early axial patterning

Establishment of CNS organizers

Regulation of CNS neurogenesis

Cell-type specificity in the CNS

Maintenance of continuous CNS neurogenesis

Formation of neural crest: A source of the PNS

Control of neural crest migration

Regulation of PNS neurogenesis

Neural connectivity: Pathfinding and synaptogenesis

Conclusions

References

22 Wnt Signaling in Heart Organogenesis

Introduction

Canonical Wnt/β-catenin signaling has multiphasic roles in heart muscle differentiation

Noncanonical Wnt/JNK signaling supports cardiac specification, morphogenesis, and terminal differentiation

Wnt signaling in heart muscle regeneration

Conclusions

References

23 Wnt Signaling in Kidney Organogenesis

Introduction

Development of the nephron

Development of the collecting duct system

Development of the renal medulla

Summary and future outlook

References

24 Wnt Signaling Regulation of Tissue Architecture (EMT and MET) and Morphogenesis:

Introduction

Wnt signaling pathways

Tumor growth and progression (metastasis)

Wnt signaling in CRC morphogenesis

Wnt signaling in liver cancer

Perspectives

Acknowledgement

References

25 Wnt Signaling in Adult Stem Cells:

What are adult stem cells?

The stem cell niche concept

The prototypical stem cell: The hematopoietic stem cell (HSC)

Intestinal stem cells

Skin stem cells

Wnt signaling in intestinal stem cells

Wnt signaling in hematopoietic stem cells

Concluding remarks

References

26 Restoring Tissue Homeostasis:

Introduction

Planarian whole-body regeneration

Lower vertebrate appendage regeneration

Liver regeneration

Skeletal muscle regeneration

Kidney regeneration

Are there common principles of Wnt function in regenerative processes?

Acknowledgments

References

Part 4: Wnt Signaling in Chronic Disease

27 Wnt Signaling and Colorectal Cancer

Introduction

Apc loss induces a crypt progenitor cell-like phenotype in an animal model