Preface T HIRTY YEARS AGO, BETTY HAY ORGANIZED AN INFLUENTIAL VOLUME on the extracellular matrix (ECM) that emphasized the biological effects of the ECM on cells. 1 That timely book recognized an increasing emphasis on biology in a field that had been dominated previously by biochemical and structural analyses. It was published just prior to the beginning of the impact of molecular biology on studies of ECM proteins and, during the past 30 years, we have witnessed several major transformations in our ability to understand the biology as well as the biochemistry and struc- ture of the ECM and its molecular constituents. Among the transformational advances that one can list are molecular biology, the use of genetically engineered mice, the sequencing of multiple genomes, progress in the genetics of ECM-based diseases, and advances in imaging of cells in culture and in intact animals. These advances have led to a much more profound understanding of the roles of ECM in biological processes. The original Hay volume served as a valuable resource for the field and was followed by a second edition 10 years later. 2 We felt that the time was ripe for an updated overview of the biology of ECM, and we agreed to take on this challenge when Richard Sever at Cold Spring Harbor Laboratory Press invited us to do so. Given the ubiquity and complexity of ECMs and the enormous advances made, this was indeed a daunting task. One cannot expect to cover, in a single volume, all that we now know about ECMs, the molecules that they contain, and the myriad effects that they have upon cel- lular behavior. So, although we have not attempted to assemble a complete treatise on ECMs and theirconstituents, we have endeavored to illustrate the manifold aspects of ECM biology. The first seven chapters review the overall composition and some of the major and best under- stood components of the ECM: collagens, proteoglycans, and major glycoproteins. In each case, the biochemical and structural data are linked to biological functions and in many cases to human dis- eases. The first chapter gives an overview of the diversity of ECM proteins as revealed by genomic analyses, which provides a reasonably complete picture of the universe of ECM proteins. Basement membranes and their constituents (laminins, type IV collagen, nidogens, and perlecan) are reviewed by Yurchenco with emphasis on assembly of basement membranes, a key form of ECM universal to all metazoa. Ricard-Blum discusses the many forms of collagen and their assembly into a variety of fibrils. Both chapters discuss the cellular receptors that interact with these forms of ECM. Sarrazin et al. review the important functions of heparan sulfate proteoglycans and their inter- actions with soluble factors and with cell-surface receptors. The following three chapters cover three of the most intensively studied ECM glycoprotein families: thrombospondins (Adams and Lawler), tenascins (Chiquet-Ehrismann and Tucker), and fibronectins (Schwarzbauer and DeSimone). Each of these families of glycoproteins has particular biologically interesting featuresthat collectively illus- trate very well the diversity of ECM functions across almost all of biology. Implicit in the concept that the ECM helps to regulate cellular behavior is a requirement for cel- lular receptors to receive, interpret, and transmit the inputs. At the time of the first Hay volume, we did not have any idea how cells recognize ECM, and it was not until the mid-1980s that the molecular nature of ECM receptors became clear. The most prominent ECM receptors are integrins, present in 1 Hay ED, ed. 1981. Cell biology of extracellular matrix. Plenum, New York. 2 Hay ED, ed. 1991. Cell biology of extracellular matrix, 2nd ed. Plenum, New York. vii Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
12
Embed
i-viii cshperspect-ECM-FM 1. · some of these processesand the involvement of the ECM. Matrix structure is not static; it is, in fact, very dynamic and the remodeling of the ECM plays
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Preface
THIRTY YEARS AGO, BETTY HAY ORGANIZED AN INFLUENTIAL VOLUME on the extracellular matrix (ECM)that emphasized the biological effects of the ECM on cells.1 That timely book recognized an
increasing emphasis on biology in a field that had been dominated previously by biochemical andstructural analyses. It was published just prior to the beginning of the impact of molecularbiology on studies of ECM proteins and, during the past 30 years, we have witnessed severalmajor transformations in our ability to understand the biology as well as the biochemistry and struc-ture of the ECM and its molecular constituents. Among the transformational advances that one canlist are molecular biology, the use of genetically engineered mice, the sequencing of multiplegenomes, progress in the genetics of ECM-based diseases, and advances in imaging of cells inculture and in intact animals. These advances have led to a much more profound understandingof the roles of ECM in biological processes.
The original Hay volume served as a valuable resource for the field and was followed by a secondedition 10 years later.2 We felt that the time was ripe for an updated overview of the biology of ECM,and we agreed to take on this challenge when Richard Sever at Cold Spring Harbor LaboratoryPress invited us to do so. Given the ubiquity and complexity of ECMs and the enormous advancesmade, this was indeed a daunting task. One cannot expect to cover, in a single volume, all that we nowknow about ECMs, the molecules that they contain, and the myriad effects that they have upon cel-lular behavior. So, although we have not attempted to assemble a complete treatise on ECMs andtheir constituents, we have endeavored to illustrate the manifold aspects of ECM biology.
The first seven chapters review the overall composition and some of the major and best under-stood components of the ECM: collagens, proteoglycans, and major glycoproteins. In each case, thebiochemical and structural data are linked to biological functions and in many cases to human dis-eases. The first chapter gives an overview of the diversity of ECM proteins as revealed by genomicanalyses, which provides a reasonably complete picture of the universe of ECM proteins.Basement membranes and their constituents (laminins, type IV collagen, nidogens, and perlecan)are reviewed by Yurchenco with emphasis on assembly of basement membranes, a key form ofECM universal to all metazoa. Ricard-Blum discusses the many forms of collagen and their assemblyinto a variety of fibrils. Both chapters discuss the cellular receptors that interact with these forms ofECM. Sarrazin et al. review the important functions of heparan sulfate proteoglycans and their inter-actions with soluble factors and with cell-surface receptors. The following three chapters cover threeof the most intensively studied ECM glycoprotein families: thrombospondins (Adams and Lawler),tenascins (Chiquet-Ehrismann and Tucker), and fibronectins (Schwarzbauer and DeSimone). Eachof these families of glycoproteins has particular biologically interesting features that collectively illus-trate very well the diversity of ECM functions across almost all of biology.
Implicit in the concept that the ECM helps to regulate cellular behavior is a requirement for cel-lular receptors to receive, interpret, and transmit the inputs. At the time of the first Hay volume, wedid not have any idea how cells recognize ECM, and it was not until the mid-1980s that the molecularnature of ECM receptors became clear. The most prominent ECM receptors are integrins, present in
1Hay ED, ed. 1981. Cell biology of extracellular matrix. Plenum, New York.2Hay ED, ed. 1991. Cell biology of extracellular matrix, 2nd ed. Plenum, New York.
vii
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
all metazoa and on virtually all cells. These are complex receptors, transmitting signals both into andout of cells and mediating the effects of ECM on cells and vice versa, so we have included a series ofchapters covering their properties. Integrin structure and activation are reviewed by Campbell andHumphries, their ability to activate TGF-b through interactions with fibrillins and the latentTGF-b binding proteins in the ECM are covered by Munger and Sheppard, and their roles in assem-bling complex intracellular protein complexes with both structural and signal transduction functionsare discussed by Geiger and Yamada. Wickstrom et al. illustrate the insights that can be gained fromstudies in mutant animals and contrast integrin connections to the actin-based cytoskeleton withthose to intermediate filaments. These chapters lay the ground for considering the roles of inte-grin–ECM interactions involved in mechanotransduction (Schwartz) and in cell migration(Huttenlocher and Horwitz).
One of the prime reasons for interest in ECM proteins and their receptors comes from their rolesin diverse biological processes, and the last third of this volume comprises a set of chapters addressingsome of these processes and the involvement of the ECM. Matrix structure is not static; it is, in fact,very dynamic and the remodeling of the ECM plays an important role in development, physiology,and pathology (Lu et al. and Brown). Specific biological contexts in which ECM functions are par-ticularly important are illustrated by angiogenesis (Senger and Davis), the nervous system (Barroset al.), normal and diseased skin (Watt and Fujiwara), and hemostasis and thrombosis (Bergmeierand Hynes). Each of these chapters illustrates different aspects of ECM functions.
Collectively, these chapters encompass the diverse roles of ECM proteins, their effects on cells,and their importance in human diseases. Our increased understanding of the details of ECM struc-ture and function coming from biochemistry; cellular, molecular, and structural biology; genetics;and genomics has confirmed their importance in the behavior of virtually all cells. Even erythrocytes,arguably the prototypical nonadherent cell type, have key interactions with the ECM during theirdevelopment. It has become clear that cell–ECM interactions and receptors are at least as importantas those between soluble ligands (hormones, growth factors, cytokines) and their receptors. Indeed,many so-called soluble ligands actually function as ECM-bound solid-phase ligands, and many ofthem are completely dependent on concomitant input from ECM adhesion receptors. The centralroles in development of the ECM suggested long ago by embryologists such as Clifford Grobsteinhave been amply confirmed, and there are preliminary indications that fundamental aspects of devel-opment and homeostasis, such as morphogen gradients and stem cell niches, rely on ECM involve-ment. Many human diseases arise from mutations in genes encoding ECM proteins as recognized byVictor McKusick, and cell-matrix adhesion and signaling are also affected in many autoimmune dis-eases. These important and fascinating topics are increasingly understood as we uncover the detailsof cell–ECM interactions and their perturbations in disease. Drugs targeting ECM interactions arealready in use in the clinic for many diseases, and it is evident that many other potential therapies willemerge from ongoing research. We hope that this collection of reviews by experts in the field will serveto promote research leading to discoveries and applications based on improved understanding of theroles of the ECM constituents, their interactions, and their receptors.
RICHARD O. HYNES
KENNETH M. YAMADA
July 2011
Preface
viii
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
overview, 314–315remodeling of extracellular matrix during vascular
tube formation and stabilization
MT1-MMP and formation of vascular guidancetunnels, 325–326
pericyte recruitment and vascular basementmembrane assembly within vascularguidance tunnels, 326–327
thrombospondin function in endothelial cells, 110Apical ectodermal ridge (AER), 287–288ApoER2, 336Arp2/3, 266–267Aspirin, 383
Axon. See Neuron
BBasement membrane
brain development, 33epidermal-dermal junction, 31–32glomerular development and filtration, 30–31morphogenesis, 29–30
nephronectin, 28netrins, 28papilin, 29pericyte recruitment and vascular basement
membrane assembly within vascular
guidance tunnels, 326–327
389
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
trimerization domains, 51triple helix, 48
superfamily, 45–48type I
structure, 3vascular cord formation, 316–318
type IV collagen in basement membranelaminin-nidogen complex binding, 25–26stabilization, 26–27
supramolecular architecture, 18–19type VI function, 28type VII function, 56type XIII function, 56–57type XV function, 28
type XVIII. See also Heparan sulfateproteoglycans, 70
function, 27–28, 66mutant phenotypes, 70, 84
type XXIV function, 56type XXVII function, 52, 56
COMP. See ThrombospondinsConnective tissue growth factor (CTGF), fibrosis role,
364
Crk, adhesion regulation, 2CSPGs. See Chondroitin sulfate proteoglycansCTGF. See Connective tissue growth factorCytochalasin D, 212Cytoskeleton. See Actin
DDDD motif, 107
DDR. See Discoidin domain receptorDermal papilla (DP), 362Development
basement membrane early morphogenesis, 29–30brain basement membranes, 33
composition changes in extracellular matrix, 302defining of extracellular matrix, 299–300diffusion in extracellular matrix formation,
300–301epithelial branch patterning and extracellular matrix
DP. See Dermal papillaDystroglycan, 11, 23, 25, 337
EEB. See Epidermolysis bullosaEC. See Endothelial cellEDA. See Extra domain AEGF. See Epidermal growth factorEHS sarcoma. See Engelbreth-Holm-Swarm sarcoma
Elasticity, extracellular matrix, 203, 285–286EMT. See Epithelial–mesenchymal transitionEna, 251Endothelial cell (EC). See also Angiogenesis
extracellular matrix role in proliferation, survival,
and migration, 315–316thrombospondin function, 110vascular endothelium, 372
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
Fibroblast growth factors (FGFs) (Continued)extracellular matrix binding, 27, 285heparan sulfate proteoglycan binding, 76–78skeletal development and remodeling, 288
Fibronectinsadhesions, 205–206, 212–213assembly of fibrils
deoxycholate insolubility, 9, 155–156developmental mechanisms and consequences
of assembly, 156–160monomer–monomer interactions, 154overview, 153–154receptor requirements and intracellular
connections, 154–155
deoxycholate insolubility, 9, 155–156domain organization and isoforms, 150–151modules, 149–150phylogeny, 13–14
prospects for study, 160–161splice variants, 151–152
Focal adhesion. See AdhesionsFocal adhesion kinase (FAK)
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
Latent transforming growth factor-b binding protein(LTBP). See Transforming growthfactor-b
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
Nidogen, laminin complex and linkage to type IVcollagen, 25–26
Nitric oxide (NO), thrombospondin and signalingantagonism, 110–111
NMJ. See Neuromuscular junctionNO. See Nitric oxideNoggin, 362Notch, 109
OOligodendrocyte precursor cell (OPC), 340OPC. See Oligodendrocyte precursor cell
Osteoblast, thrombospondin function, 111
PPAK, 268Papilin, basement membrane function, 29PCP. See Planar cell polarityPDGF. See Platelet-derived growth factorPericyte, recruitment and vascular basement membrane
assembly within vascular guidancetunnels, 326–327
Perlecan. See also Heparan sulfate proteoglycanslinkage to cell surface, 26mutant phenotypes, 69
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
SRF, 361SSS. See Stiff skin syndromeStem cell
differentiation and extracellular matrix dynamics,
290–291epidermal stem cell
integrin–extracellular matrix interactionregulation of stem cell fate, 361–362
markers, 359–361
heparan sulfate proteoglycans in niche, 84–85neural stem cell. See Neuron
Stiff skin syndrome (SSS), 187, 191Syndecans. See also Heparan sulfate proteoglycans
coreceptor activity, 79–81
development role, 82fibrillogenesis role, 155integrin interactions, 76, 81mutant phenotypes, 67–68
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
WWASP, 265Wnt, fibrillogenesis regulation in development,
159–160Wound healing
cancer similarity, 366epidermal hyperproliferation, 363–364fibrin clot cellular interactions, 382
ZZyxin, force signaling, 250–251
Index
397
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.
Copyright 2012 Cold Spring Harbor Laboratory Press. Not for distribution. Do not copy without written permission of Cold Spring Harbor Laboratory Press.