GPI Membrane Anchors-The Much Needed Link


by

John A. Dangerfield

DOI: 10.2174/97816080512361100101
eISBN: 978-1-60805-123-6, 2010
ISBN: 978-1-60805-375-9

  
  


Indexed in: Scopus, Chemical Abstracts

This Ebook aims to review basic understandings and give current opinions about several important aspects of glycosylphosphatidylinosit...[view complete introduction]
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Table of Contents

Foreword , Pp. i

Brian Salmons

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Preface , Pp. ii

John A. Dangerfield and Christoph Metzner

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Contributors , Pp. iii-iv (2)

John A. Dangerfield and Christoph Metzner

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GPI-Anchored Proteins and Their Cellular Surroundings: Signalling, Function and Medical Implications of Membrane Microdomains , Pp. 1-18 (18)

Vera Michel, David W.L. Ma and Marica Bakovic

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Trans-Cellular Mobility of GPI-Anchored Proteins , Pp. 19-33 (15)

Barbara Viljetic, Marija Heffer-Lauc and Gordan Lauc

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GPI-Anchored Proteins: Biophysical Behaviour and Cleavage by Pi-Specific Phospholipases , Pp. 34-52 (19)

Frances. J. Sharom

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Proteomic Approaches for GPI-Anchored Protein Analysis , Pp. 53-63 (11)

Miren J. Omaetxebarria and Felix Elortza

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Chemical Synthesis, Modification and Mimicry of the GPI Anchor , Pp. 64-82 (19)

Martin J. Lear, Bastien Reux and Karthik Sekar

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Surface Engineering of Biomembranes with GPI-Anchored Proteins and its Applications , Pp. 83-97 (15)

Christoph Metzner, Daniel F. Legler and John A. Dangerfield

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Glossary , Pp. 98-102 (5)

John A. Dangerfield and Christoph Metzner

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Index , Pp. 103-104 (2)

John A. Dangerfield and Christoph Metzner

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Foreword

In the early 90’s, gene therapists were beginning to get their heads around the concept of targeted delivery as a means to improve safety and efficacy of gene therapy. Retroviral vectors were, at that time, the most promising vehicles for gene delivery, having been successfully used in the first clinical trials. Naturally, the targeting of retroviral vectors was at the forefront of research, in particular at the level of infection as pointed out in one of the first reviews on this area written by Walter Gunzburg and myself and appearing in Human Gene Therapy. Although an important new concept at the time, it all turned out to be a lot more complicated from today’s standpoint.

The modification of virus envelopes fascinated John Dangerfield – he saw viruses as boats that could be equipped with off board ATP driven motors or magnetised by the attachment of iron particles. All very science fiction, I thought, a sort of minaturised lego or mechano set enabling functionalised viruses to be steered so that they deliver their cargo of therapeutic genes to distant ports of damaged or defective cells in the body. Of course, the overriding problem was how to attach these molecules to the virus membrane...

Fast forward to today, and we have a book edited by John and former student and colleague Christoph Metzner, about GPI membrane anchors, a molecular tag that helps insert proteins into the plasma membrane of cells and not just anywhere but in so called lipid rafts, agglomerations or islands of lipid that float in the plasma membrane. The book covers a wide variety of aspects of GPI anchors, what they are, their structure, how they function, what roles they carry out, how they can be used as a tool in biotechnology and how similar GPI-like molecules can be created by molecular mimicry. John and Christoph have selected some of the world’s foremost authorities on GPI anchors to contribute chapters to this book. These highly skilled authors provide not only reviews of the knowledge that has been gained about GPI anchors over the last decade or two but also protocols on how to isolate and modify such molecules. Thus the book can be viewed as a nuts and bolts engineering manual and cook book – a kind of “all you ever wanted to know” guide. All in all, the authors have made excellent selections showcasing various facets of current GPI research and shown remarkable editorial skills as well as contributing significant progress themselves to this field.

So why start this foreword with ruminations about the targeting of enveloped viruses like retroviruses? Well GPI anchors offer a solution for the insertion of all kinds of proteins into the plasma membrane not only of cells but also of enveloped viruses and that offers a means to attach ATP motors, magnetic particles and almost any other nanomolecule. This technology, which has been termed “virus painting”, but can also be viewed as a type of decorating or coating of enveloped virions, holds much promise for the targeting of safer virus vectors and vaccines as well as having uses in the diagnosis of well-known and emerging virus diseases.

Dr. Brian Salmons, President and CEO of SGAUSTRIA


Preface

Developing technologies over the best part of the last 40 years have allowed scientists to continually re-address the way cholesterol-rich cell membrane microdomains, or lipid rafts, and their protein components are analysed. More recently this accumulated knowledge has started to take shape into substantial structures of understanding. The focus of this work is on glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-AP) as a major component of lipid rafts. As a special feature, detailed lab-protocols are helpfully integrated into the text in order to allow the replication of state-of-the-art experiments.

The first 2 chapters are of an introductory nature. Firstly, Vera Michel and co-authors review the biological relevance of lipid rafts, what their absence can mean in terms of pathologies and introduce them as "the home of GPI-AP" whereas Barbara Viljetić and co-authors then go into more detail on the basics of GPI-AP. This second chapter has an interesting focus on the mechanisms and reasons for different types of protein release, both with and without their GPI-anchor, as well as their uptake and effect on surrounding cells. Taken together, they give a sound foundation of understanding before going onto the subsequent chapters.

In chapter 3, Frances Sharom gives her interesting insight on the biophysics of the way membranes, GPI-proteins, their anchors and cutting enzymes influence each other, with important implications for function of GPI-AP and their releasing enzymes. In chapter 4, Miren Omaetxebarria and co-authors have a strong technical focus as they take a proteomics approach to analysing GPI-AP, which is rounded up with a look at the bioinformatics aspect. This includes information of the analysis of proteins, anchors (glycans) and the definition of GPI-anchor attachment or omega-sites.

Taking another turn in chapter 5, Martin Lear and co-authors introduce the chemistry of GPIs. Natural GPI-anchors are diverse in structure and yields from cells are low, so the chemical synthesis of GPI-mimics is interesting and may be crucial for up-scaling for multiple applications. This synthetic approach discusses far reaching aspects of the topic and is presented in a way that is accessible for the biological audience. Finally, in chapter 6, the editors, together with Daniel Legler, show that cells, viruses and other biomembrane-encompassed particles can be decorated on their surface with GPI-AP, a process known as "GPI painting" which does not require any genetic manipulation of the modified entities. They further discuss the already emerging applications for this technology.

Aside from addressing the potential that GPI-AP have in perspective of today's developing biomedical and biotechnological scene, one of the aims of this book is to draw together the various scientific disciplines within which GPI-AP and related topics are being researched. Each discipline can of course be justified in its own right; however, by enabling a common level of understanding, novelties may be revealed that allow extraordinary progress to be made.

John A. Dangerfield and Christoph Metzner

List of Contributors

Editor(s):
John A. Dangerfield
Christian Doppler Laboratory
Austria & Singapore




Co-Editor(s):
Christoph Metzner
University of Veterinary Medicine
Austria




Contributor(s):
Marica Bakovic
Department of Human Health and Nutritional Sciences
Animal Science and Nutrition Building, Room 346, University of Guelph
Guelph
ON, N1G 2W1
Canada


John A. Dangerfield
Department of Pathobiology
Institute of Virology, Christian Doppler Laboratory for Gene Therapeutic Vector Developtment, University of Veterinary Medicine
A-1210 Vienna
#05-518 Centros, 20 Biopolis Way
Cambridge, 138668
Austria


Felix Elortza
Proteomics Core Facility
CIC bioGUNE, Building 801, Technology Park of Bizkaia
Derio, 48160
Spain


Marija Heffer-Lauc
Department of Medical Biology
J.J. Strossmayer University, School of Medicine
J. Huttlera 4
Osijek
HR, 31000
Croatia


Gordan Lauc
Department of Medical Chemistry and Biochemistry
J.J. Strossmayer University School of Medicine, J. Huttlera 4
Osijek
HR, 31000
Croati


Martin J. Lear
Department of Chemistry, Faculty of Science and Medicinal Chemistry Programme,
Life Sciences Institute, 3 Science Drive 3, National University of Singapore
Cambridge, 117543
Singapore


Daniel F. Legler
Biotechnology Institute Thurgau (BITg), University of Konstanz
Unterseestrasse 47
Kreuzlingen
CH, 8280
Switzerlan


David W.L. Ma
Department of Human Health and Nutritional Sciences
Animal Science and Nutrition Building, Room 243, University of Guelph, Guelph
Cambridge
ON, N1G 2W1
Canada


Christoph Metzner
Department of Pathobiology
Institute of Virology, University of Veterinary Medicine
Vienna
A, 1210
Austria


Vera Michel
Department of Human Health and Nutritional Sciences
Animal Science and Nutrition Building, Room 309, University of Guelph
Guelph
ON, N1G 2W1
Canada


Miren J. Omaetxebarria
Department of Biochemistry and Molecular Biology
Faculty of Science and Technology, Bizkaia Campus, University of The Basque Country, Sarriena z/g
The Basque Country, 48940
Spain


Bastien Reux
Department of Chemistry, Faculty of Science and Medicinal Chemistry Programme
Life Sciences Institute, 3 Science Drive 3, National University of Singapore
Singapore


Karthik Sekar
Department of Chemistry, Faculty of Science and Medicinal Chemistry Programme
Life Sciences Institute, 3 Science Drive 3, National University of Singapore
Singapore


Frances J. Sharom
Department of Molecular and Cellular Biology
University of Geulph
ON, N1G 2W1
Canada


Barbara Viljetic
Department of Medical Chemistry and Biochemistry
J.J. Strossmayer University School of Medicine, J. Huttlera 4
Osijek
HR, 31000
Croatia




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