Molecular Aspects of the Stress Response: Chaperones, Membranes and Networks

ADVANCES m EXPERIMENTAL MEDICINE AND BIOLOGY

Editorial Board:

NATHAN BACK, State University of New York at Buffalo

IRUN R. COHEN, The Weizmann Institute of Science

DAVID KRITCHEVSKY, Wistar Institute

ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research

RODOLFO PAOLETTI, University of Milan

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Edited by Peter Csermely and Laszlo Vigh

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Molecular Aspects of the Stress Response: Chaperones, Membranes and Networks Edited by

Peter Csermely

Department of Medical Chemistry, Semmelweis University, Budapest, Hungary

Laszlo Vigh

Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary

Springer Science+Business Media, LLC Landes Bioscience / Eurekah.com

Springer Science+Business Media, LLC Landes Bioscience / Eurekah.com

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Molecular Aspects of the Stress Response: Chaperones, Membranes and Networks, edited by Peter Csermely and Laszl6 Vigh, Landes Bioscience / Eurekah.com / Springer Science+Business Media, LLC dual imprint / Springer series: Advances in Experimental Medicine and Biology

ISBN-10: 0-387-39974-7 ISBN-13: 978-0-387-39974-4

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PREFACE

We are extremely happy to present the reader this book containing a summary of a well-known research field, the phenomenon of cellular stress defense from two new angles: networks and membranes. The volume starts with an introduction to the concept of molecular chaperones in their original sense: R. John Ellis, the founder of the chaperone concept describes chaperones as mediators of correct assembly and/or misassembly of other macromolecular complexes. This sets the tone of the book, where later chapters give detailed examples of the richness of chaperone ac­tion by hundreds of other proteins and membrane structures.

The reader will learn the role of chaperone classes such as Hsp27 or Hsp90, the action of highly organized chaperone networks in various cellular compartments such as the ER or mitochondrial/ER networks as well as the molecular details of the signaling mechanisms leading to chaperone induction during stress. Various special stress defense mechanisms against oxidative stress or dryness will also be covered.

Membranes comprise a surprising mixture of stability and dynamics in the cell. Their role in the regulation of the stress response has been accepted only slowly in the field. Two chapters summarize this important aspect of the stress response showing the importance of membrane hyperstructures, lipid species composition, protein/ membrane interactions and cold adaptation.

Protein aggregation is a typical example of protein misassembly leading to dev­astating consequences. The book gives a summary of both the molecular mecha­nisms protecting against aggregation as well as the consequences of protein aggre­gation in neurodegenerative diseases and aging.

Chaperones modulate not only individual protein complexes and their hosting cells, but also have profound effects on complex cellular networks, such as the im­mune system or on the phenotype of whole organisms regulating their development and evolution.

We believe the reader will be also convinced after studying the chapters of this book and checking some of the vast number of original references that chaperones play a key role in the organization of various molecular, organellar and cellular networks efficiently shaping their emergent properties at even higher levels. This story is just at the beginning, opening a wide range of possibilities for efficient applications in the medical treatment of diseases and aging.

Budapest - Szeged, August 2006 Peter Csermely and Ldszlo Vigh

ABOUT THE EDITORS-

PETER CSERMELY (48) is a professor at the Semmelweis Uni­versity (Budapest, Hungary). His major fields of study are molecular chap-erones (www.chaperone.sote.hu) and networks (www.weaklink.sote.hu). In 1995 Dr. Csermely launched a highly successful initiative, which pro­vides research opportunities for more than 10,000 gifi:ed high school students (www.nyex.info). He wrote and edited ten books (including Weak Links at Springer in 2006) and has published 200 research papers with total citations over 2000. Dr. Csermely is the Vice President of the Hungarian Biochemical Society, the President of Cell Stress Society In­ternational, an Ashoka Fellow, was a Fogarty and Howard Hughes Scholar and received several other national and international honors and awards including the 2004 Descartes Award of the European Union for Science Communication.

L A S Z L C V I G H (56) is a member of the Hungarian Academy of Sciences (2004) and of the European Academy of Sciences (2002) at Brussels, in the Biomedical Sciences section. He is an honorary professor at Szeged University (2005). He leads the Molecular Stress Biology research group at the Institute of Biochemistry, Biological Research Centre (BRC) of the Hungarian Academy of Sciences at Szeged. The BRC has been a Centre of Excellence of the European Union since 2000. For his out­standing work in lipid-membrane and stress research. Professor Vigh was awarded the highest State Prize for Science in Hungary, the "Szechenyi Award", in 1998. He was the Director of his Institute from 1994 to 2004. He has over 140 publications with total citations over 2200.

PARTICIPANTS

Julius Anckar Department of Biology Abo Akademi University and Turku

Centre for Biotechnology University of Turku and Abo

Akademi University Turku Finland

Frank Boellmann Carolina Cardiovascular

Biology Center School of Medicine University of North Carolina Chapel Hill, North Carolina U.S.A.

Andre-Patrick Arrigo Laboratoire Stress Oxydant Chaperons et Apoptose CNRS UMR 5534 Centre de Genetique Moleculaire

et Cellulaire Universite Claude Bernard Lyon-1 Villeurbanne France

Gabor Balogh Institute of Biochemistry Biological Research Center of the

Hungarian Academy of Sciences Szeged Hungary

Gregory L. Blatch Chaperone Research Group Department of Biochemistry,

Microbiology and Biotechnology Rhodes University Grahamstown South Africa

Heather R. Brignull Department of Biochemistry,

Molecular Biology and Cell Biology Rice Institute for Biomedical Research Northwestern University Evanston, Illinois U.S.A.

Andrew R. Cossins School of Biological Sciences Liverpool University The Biosciences Building Liverpool U.K.

John H. Crowe Section of Molecular

and Cellular Biology University of California Davis, California U.S.A.

Participants

Peter Csermely Department of Medical Chemistry Semmelweis University Budapest Hungary

R. John Ellis Department of Biological Sciences University of Warwick Coventry CV4 7AL U.K.

Attila Glatz Institute of Biochemistry Biological Research Center of the

Hungarian Academy of Sciences Szeged Hungary

Pierre Goloubinoff DBMV Faculty of Biology and Medicine University of Lausanne Lausanne Switzerland

Andrew Y. Gracey School of Biological Sciences Liverpool University The Biosciences Building Liverpool U.K.

Scott A.L. Hayward School of Biological Sciences Liverpool University The Biosciences Building Liverpool U.K.

Linda M. Hendershot Department of Genetics and Tumor

Cell Biology St. Jude Children's Research Hospital Memphis, Tennessee U.S.A.

Marie-Pierre Hinault DBMV Faculty of Biology and Medicine University of Lausanne Lausanne Switzerland

Ibolya Horvath Institute of Biochemistry Biological Research Center of the

Hungarian Academy of Sciences Szeged Hungary

Walid A. Houry Department of Biochemistry University of Toronto Toronto, Ontario Canada

Jennifer R. Knapp Division of Basic Sciences Fred Hutchinson Cancer

Research Center Seattle, Washington U.S.A.

Jacques Landry Centre de recherche en cancerologie

de rUniversite Laval L'Hotel-Dieu de Quebec Quebec Canada

Participants

Richard I. Morimoto Department of Biochemistry,

Molecular Biology and Cell Biology Rice Institute for Biomedical Research Northwestern University Evanston, Illinois U.S.A.

James F. Morley Department of Biochemistry,

Molecular Biology and Cell Biology Rice Institute for Biomedical Research Northwestern University Evanston, Illinois U.S.A.

Patricia A. Murray School of Biological Sciences Liverpool University The Biosciences Building Liverpool U.K.

Sebastien Ian Nadeau Centre de recherche en cancerologie

de rUniversite Laval L'Hotel-Dieu de Quebec Quebec Canada

Rosario Rizzuto Department of Experimental

and Diagnostic Medicine University of Ferrara Ferrara Italy

Suzannah Rutherford Division of Basic Sciences Fred Hutchinson Cancer

Research Center Seattle, Washington U.S.A.

Yuichiro Shimizu Department of Genetics and Tumor

Cell Biology St. Jude Children's Research Hospital Memphis, Tennessee U.S.A.

Lea Sistonen Department of Biology Abo Akademi University and Turku

Centre for Biotechnology University of Turku and Abo

Akademi University Turku Finland

Stefano Piotto Department of Chemical

and Food Engineering University of Salerno Fisciano-Salemo Italy

Zoltan Prohaszka Ilird Department of Internal Medicine Semmelweis University Budapest Hungary

Csaba Soti Department of Medical Chemistry Semmelweis University Budapest Hungary

Gyorgy Szabadkai Department of Experimental

and Diagnostic Medicine University of Ferrara Ferrara Italy

Participants

Zsolt Torok Institute of Biochemistry Biological Research Center of the

Hungarian Academy of Sciences Szeged Hungary

Laszlo Vigh Institute of Biochemistry Biological Research Center of the

Hungarian Academy of Sciences Szeged Hungary

Richard Voellmy HSF Pharmaceuticals SA Pully Switzerland

Rongmin Zhao Department of Biochemistry University of Toronto Toronto, Ontario Canada

CONTENTS

1. PROTEIN MISASSEMBLY: MACROMOLECULAR CROWDING AND MOLECULAR CHAPERONES 1

R. John Ellis

Introduction 1 Inside the CeU 1 The Principle of Protein Self-Assembly: Yesterday and Today 3 The Molecular Chaperone Concept 4 The Problem of Protein Misassembly 6 Macromolecular Crowding 7 Stimulation of Misassembly by Crowding Agents 10 How do Chaperones Combat Misassembly? 11 The Molecular Chaperone Function 11

2. THE CELLULAR "NETWORKING" OF MAMMALLVN HSP27 AND ITS FUNCTIONS IN THE CONTROL OF PROTEIN FOLDING, REDOX STATE AND APOPTOSIS 14

Andre-Patrick Arrigo

Introduction 14 Hsp27 in Cells Exposed to Heat Shock 15 Hsp27 in Cells Exposed to Oxidative Stress 17 Hsp27 in Cells Committed to Apoptosis 19 Conclusions and in Vivo Perspectives 21

3. MOLECULAR INTERACTION NETWORK OF THE HSP90 CHAPERONE SYSTEM 27

Rongmin Zhao and Walid A. Houry

Introduction 27 Mapping the Hsp90 Physical Interaction Network 29 Mapping the Hsp90 Genetic Interaction Network 30 The Hsp90 Interactome 31 Perspectives and Future Directions 34

xiv Contents

4. ORGANIZATION OF THE FUNCTIONS AND COMPONENTS OF THE ENDOPLASMIC RETICULUM 37

Yuichiro Shimizu and Linda M. Hendershot

Introduction 37 Overview of Protein Biosynthesis in the ER 37 The ER Possesses a Unique Environment for Protein Folding 39 The ER Quality Control System 39 Chaperone Selection during Protein Maturation in the ER 41 Organization of a Subset of Chaperones into Large

Preformed Complexes 42 Components of the Calnexin/Calreticulin System

and Their Organization 43 Possible Advantages and Constraints That an Organization

of ER Chaperones Might Impose 44

5. MOLECULAR CRIME AND CELLULAR PUNISHMENT: ACTIVE DETOXIFICATION OF MISFOLDED AND AGGREGATED PROTEINS IN THE CELL BY THE CHAPERONE AND PROTEASE NETWORKS 47

Marie-Pierre Hinault and Pierre Goloubinoff

The Criminal Nature of Protein Aggregation in the Cell 47 Defence Mechanisms against Protein Aggregation in the Cell 48 Aging and Conformational Diseases: Failures of Law Enforcement

Leading to Lawlessness 52

6. CHAPERONES AS PARTS OF CELLULAR NETWORKS 55

Peter Csermely, Csaba Soti and Gregory L. Blatch

Introduction: Cellular Networks and Chaperones 55 Chaperones in Cellular Networks 58 Chaperone-Mediated Emergent Properties of Cellular Networks 59 Chaperone Therapies 60 Conclusion 60

7. CHAPERONES AS PARTS OF ORGANELLE NETWORKS 64

Gyorgy Szabadkai and Rosario Rizzuto

Introduction 64 Biogenesis of the ER and Mitochondrial Networks:

A Role for Chaperones in Interorganellar Communication? 65 ER-Mitochondrial Ca ^ Transfer: A Major Example of Organelle Interactions 67

Contents xv

Chaperone Control of £R-Mitochondrial Interaction along the Ca ^ Signal Transmission Pathway 68

Perspectives: The Role of Chaperone Mediated £R-Mitochondria Coupling in Cell Death 71

Conclusions 73

8. HEAT SHOCK FACTOR 1 AS A COORDINATOR OF STRESS AND DEVELOPMENTAL PATHWAYS 78

Julius Anckar and Lea Sistonen

Introduction 78 Functional Domains of HSFl 79 Activation Mechanisms of HSFl 80 Regulation of hsp Gene Transcription by HSFl 81 Stress-Specific Activation of HSFl 82 HSFl as a Developmental Regulator 83 HSFl-Mediated Expression of Cytokines 83 Heat Shock Factors Working Together 84 Future Perspectives 85

9. CHAPERONE REGULATION OF THE HEAT SHOCK PROTEIN RESPONSE 89

Richard Voellmy and Frank Boellmann

Introduction 89 Feedback Regulation of the Heat Shock Protein Response

by Stress-Inducible Chaperones 90 Hsps and Co-Chaperones Repress Activation of HSFl 90 HSP90-Containing Multichaperone Complexes Regulate HSFl Oligomeric

Status and Transcriptional Competence 91 Regulation of HSFl by CHIP as Part of fhe Protein Quality

Control System 93 Synopsis 94

10. MECHANISMS OF ACTIVATION AND REGULATION OF THE HEAT SHOCK-SENSITIVE SIGNALING PATHWAYS 100

Sebastien Ian Nadeau and Jacques Landry

Introduction 100 Major Signaling Pathways Activate Heat Shock 101 Molecular Origin of the Heat Shock Signal 106 Conclusion 107

xvi Contents

11. MEMBRANE-REGULATED STRESS RESPONSE: A THEORETICAL AND PRACTICAL APPROACH 114

Laszlo Vigh, Zsolt Torok, Gabor Balogh, Attila Glatz, Stefano Piotto and Ibolya Horvath

Introduction 114 The Evolution of the ^'Membrane Sensor" Hypothesis with the Aid

of Unicellular Stress Models: The Beauty of Simplicity 115 Evidence Concerning the Operation of Membrane-Associated

Stress Sensing and Signaling Mechanisms in Mammalian Cells. Membrane Lipids May Provide the Molecular Switch for Stress Sensing and Signaling 119

Stress Response Profiling: Can We "Zoom In" on Membrane Hyperstructures Engaged in the Generation of Stress Signal? 122

Can We Point to Lipid Molecular Species Engaged in Stress Sensing and Signaling? 123

Computational Methods for the Design of Subtle Interactions between Lipids and Proteins of Membranes 124

Conclusions 127

12. BEYOND THE LIPID HYPOTHESIS: MECHANISMS UNDERLYING PHENOTYPIC PLASTICITY IN INDUCIBLE COLD TOLERANCE 132

Scott A.L. Hayward, Patricia A. Murray, Andrew Y. Gracey and Andrew R. Cossins

Introduction 132 Cold Adaptation and the Lipid Hypothesis 133 Evidence in Prokaryotes 133 Evidence in Plants 134 Evidence in Animals 134 Caenorhabditis elegans Cold Tolerance and the Contribution of Desaturases 135 Nonlipid Mechanisms of Cold Tolerance 137 Interaction and Compensatory Mechanisms 137 Conclusions 138

13. TREHALOSE AS A "CHEMICAL CHAPERONE": FACT AND FANTASY 143

John H. Crowe

Sugars and Stabilization of Biological Materials 143 Origins of the Trehalose Myth 144 The Mechanism of Depression of Tm 145 Trehalose Stabilizes Microdomains in Membranes 145 There Is More Than One Way to the Same End 147

Contents xvii

Trehalose Has Useful Properties, Nevertheless 147 Glass Transitions and Stability 148 Nonenzymatic Browning and Stability of the Glycosidic Bond 149 Sugar Glasses in Plant Anhydrobiotes 150 Lessons from Nature Can Be Used to Preserve Intact Cells

in the Dry State 151 Successful Freeze-Drying of Trehalose-Loaded Cells 152 Can Nucleated Cells Be Stabilized in the Dry State? 153 What Is the Role of p26 in StabUizing Dry Nucleated CeUs? 153 Summary and Conclusions 154

14. CHAPERONES AS PART OF IMMUNE NETWORKS 159

Zoltan Prohaszka

Introduction 159 Activation of Innate Immunity by Heat Shock Proteins 159 Immunological Protection of Heat Shock Proteins 160 Role of Natural Autoantibody Networks in Regulation

of Autoimmunity 161 Heat Shock Proteins as Negotiators between Promotion

of Inflammation or Control of Autoimmunity 162 Heat Shock Proteins as Elements of Multiple Networks 163

15. THE STRESS OF MISFOLDED PROTEINS: C. ELEGANS MODELS FOR NEURODEGENERATIVE DISEASE AND AGING 167

Heather R. Brignull, James F. Morley and Richard I. Morimoto

Introduction 167 Models of Neurodegenerative Disease 168 C elegans Model of polyQ Disease 168 The C. elegans polyQ Series in Neurons 169 Biophysical Properties of polyQ Proteins in Neurons of Live Animals 170 PolyQ Length-Dependent Aggregation Correlates

with Neuronal Dysfunction 172 Dynamic Biophysical Properties of Intermediate polyQ Tracts

in the Ventral Nerve Cord 173 Neuron-Specific Responses to polyQ Proteins 175 The C elegans polyQ Series in Muscle Cells 175 Aging Influences the Threshold for polyQ Aggregation and Toxicity 176 Longevity Genes Influence Aging-Dependent Aggregation

and Toxicity of polyQ Proteins 178 Genome-Wide RNAi Screening Identifies Novel Regulators

of polyQ Aggregation and Toxicity 179 Global Disruption of Folding Homeostasis by polyQ Proteins 181 Conclusion 185

xviii Contents

16. HSP90 AND DEVELOPMENTAL NETWORKS 190

Suzannah Rutherford, Jennifer R. Knapp and Peter Csermely

Introduction 190 Hidden Genetic Variation 191 Hsp90 and Signal Transduction Thresholds 193 Nonlinearity in Developmental Responses to Signal Transduction 195 A Pivotal Role for Hsp90 in Network Evolvability? 195

INDEX 199