The Extracellular Matrix: An Overview

Chapter

Abstract

The extracellular matrix encompasses the very large number of constituent macromolecules that are synthesized and secreted by cells into the space surrounding them, followed in most cases by further assembly, cross-linking, and/or polymerization of the secreted proteins to form an organized structure. The extracellular matrix has a number of critical roles in tissue and organ development, function, and repair after injury. In addition, there are numerous serious and debilitating genetic diseases whose bases lie in mutations in genes encoding extracellular matrix proteins. There are also acquired diseases, such as scurvy, chronic obstructive pulmonary disease, and cancer, that can be caused by damage to or are influenced by changes in the organization or integrity of the extracellular matrix. The goal of this chapter is to provide an overview of the extracellular matrix by discussing the different classes of extracellular matrix molecules and presenting a subset of individual extracellular matrix proteins from each class in greater detail in order to demonstrate their importance.

Keywords

Basement membrane collagen laminin proteoglycan elastic fiber bone fibrosis 

Notes

Acknowledgments

This work was supported by R01DK078314 and R01GM060432 (both to JHM).

References

  1. Arikawa-Hirasawa E, Wilcox WR, Le AH, Silverman N, Govindraj P, Hassell JR, Yamada Y (2001) Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional null mutations of the perlecan gene. Nat Genet 27:431–434CrossRefPubMedGoogle Scholar
  2. Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, von der Mark K, Wewer UM, Yamada Y, Yurchenco PD (2005) A simplified laminin nomenclature. Matrix Biol 24:326–332CrossRefPubMedGoogle Scholar
  3. Bader BL, Smyth N, Nedbal S, Miosge N, Baranowsky A, Mokkapati S, Murshed M, Nischt R (2005) Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice. Mol Cell Biol 25:6846–6856CrossRefPubMedGoogle Scholar
  4. Bolcato-Bellemin AL, Lefebvre O, Arnold C, Sorokin L, Miner JH, Kedinger M, Simon-Assmann P (2003) Laminin alpha5 chain is required for intestinal smooth muscle development. Dev Biol 260:376–390CrossRefPubMedGoogle Scholar
  5. Burgeson RE, Chiquet M, Deutzmann R, Ekblom P, Engel J, Kleinman H, Martin GR, Ortonne J-P, Paulsson M, Sanes J, Timpl R, Tryggvason K, Yamada Y, Yurchenco PD (1994) A new nomenclature for laminins. Matrix Biol 14:209–211CrossRefPubMedGoogle Scholar
  6. Burgess RW, Nguyen QT, Son YJ, Lichtman JW, Sanes JR (1999) Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction. Neuron 23:33–44CrossRefPubMedGoogle Scholar
  7. Byers PH (2000) Collagens: building blocks at the end of the development line. Clin Genet 58:270–279CrossRefPubMedGoogle Scholar
  8. Canty EG, Kadler KE (2005) Procollagen trafficking, processing and fibrillogenesis. J Cell Sci 118:1341–1353CrossRefPubMedGoogle Scholar
  9. Cho J, Mosher DF (2006) Role of fibronectin assembly in platelet thrombus formation. J Thromb Haemost 4:1461–1469CrossRefPubMedGoogle Scholar
  10. Chu ML, Tsuda T (2004) Fibulins in development and heritable disease. Birth Defects Res C Embryo Today 72:25–36CrossRefPubMedGoogle Scholar
  11. Clarke B (2008) Normal bone anatomy and physiology. Clin J Am Soc Nephrol 3(Suppl 3):S131–S139CrossRefPubMedGoogle Scholar
  12. Corson GM, Charbonneau NL, Keene DR, Sakai LY (2004) Differential expression of fibrillin-3 adds to microfibril variety in human and avian, but not rodent, connective tissues. Genomics 83:461–472CrossRefPubMedGoogle Scholar
  13. Costell M, Gustafsson E, Aszodi A, Morgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fassler R (1999) Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol 147:1109–1122CrossRefPubMedGoogle Scholar
  14. de Vega S, Iwamoto T, Nakamura T, Hozumi K, McKnight DA, Fisher LW, Fukumoto S, Yamada Y (2007) TM14 is a new member of the fibulin family (fibulin-7) that interacts with extracellular matrix molecules and is active for cell binding. J Biol Chem 282:30878–30888CrossRefPubMedGoogle Scholar
  15. Fukumoto S, Miner JH, Ida H, Fukumoto E, Yuasa K, Miyazaki H, Hoffman MP, Yamada Y (2006) Laminin alpha5 is required for dental epithelium growth and polarity and the development of tooth bud and shape. J Biol Chem 281:5008–5016CrossRefPubMedGoogle Scholar
  16. Gautam M, Noakes PG, Moscoso L, Rupp F, Scheller RH, Merlie JP, Sanes JR (1996) Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell 85:525–35CrossRefPubMedGoogle Scholar
  17. George EL, Georges-Labouesse EN, Patel-King RS, Rayburn H, Hynes RO (1993) Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 119:1079–1091PubMedGoogle Scholar
  18. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, Bousser MG, Heutink P, Miner JH, Tournier-Lasserve E, John SW (2006) Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med 354:1489–1496CrossRefPubMedGoogle Scholar
  19. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD (1997) Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 277:2002–2004CrossRefPubMedGoogle Scholar
  20. Hu Q, Reymond JL, Pinel N, Zabot MT, Urban Z (2006) Inflammatory destruction of elastic fibers in acquired cutis laxa is associated with missense alleles in the elastin and fibulin-5 genes. J Invest Dermatol 126:283–290CrossRefPubMedGoogle Scholar
  21. Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG (2003) Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. N Engl J Med 348:2543–2556CrossRefPubMedGoogle Scholar
  22. Hutter H, Vogel BE, Plenefisch JD, Norris CR, Proenca RB, Spieth J, Guo C, Mastwal S, Zhu X, Scheel J, Hedgecock EM (2000) Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes. Science 287:989–994CrossRefPubMedGoogle Scholar
  23. Hynes R (1999) Fibronectins. In: Kreis T, Vale R (eds) Guidebook to the extracellular matrix, anchor, and adhesion proteins. Oxford University Press, New York, pp 422–425Google Scholar
  24. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110:673–687CrossRefPubMedGoogle Scholar
  25. Kadler KE, Hill A, Canty-Laird EG (2008) Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators. Curr Opin Cell Biol 20:495–501CrossRefPubMedGoogle Scholar
  26. Kammerer RA, Schulthess T, Landwehr R, Schumacher B, Lustig A, Yurchenco PD, Ruegg MA, Engel J, Denzer AJ (1999) Interaction of agrin with laminin requires a coiled-coil conformation of the agrin-binding site within the laminin gamma1 chain. EMBO J 18:6762–6770CrossRefPubMedGoogle Scholar
  27. Kessler E, Takahara K, Biniaminov L, Brusel M, Greenspan DS (1996) Bone morphogenetic protein-1: the type I procollagen C-proteinase. Science 271:360–362CrossRefPubMedGoogle Scholar
  28. Khoshnoodi J, Cartailler JP, Alvares K, Veis A, Hudson BG (2006) Molecular recognition in the assembly of collagens: terminal noncollagenous domains are key recognition modules in the formation of triple helical protomers. J Biol Chem 281:38117–38121CrossRefPubMedGoogle Scholar
  29. Khoshnoodi J, Pedchenko V, Hudson BG (2008) Mammalian collagen IV. Microsc Res Tech 71:357–370CrossRefPubMedGoogle Scholar
  30. Kobayashi N, Kostka G, Garbe JH, Keene DR, Bachinger HP, Hanisch FG, Markova D, Tsuda T, Timpl R, Chu ML, Sasaki T (2007) A comparative analysis of the fibulin protein family. Biochemical characterization, binding interactions, and tissue localization. J Biol Chem 282:11805–11816CrossRefPubMedGoogle Scholar
  31. Lamande SR, Bateman JF (1999) Procollagen folding and assembly: the role of endoplasmic reticulum enzymes and molecular chaperones. Semin Cell Dev Biol 10:455–464CrossRefPubMedGoogle Scholar
  32. Le Goff C, Somerville RP, Kesteloot F, Powell K, Birk DE, Colige AC, Apte SS (2006) Regulation of procollagen amino-propeptide processing during mouse embryogenesis by specialization of homologous ADAMTS proteases: insights on collagen biosynthesis and dermatosparaxis. Development 133:1587–1596CrossRefPubMedGoogle Scholar
  33. Li DY, Faury G, Taylor DG, Davis EC, Boyle WA, Mecham RP, Stenzel P, Boak B, Keating MT (1998) Novel arterial pathology in mice and humans hemizygous for elastin. J Clin Invest 102:1783–1787CrossRefPubMedGoogle Scholar
  34. Linsenmayer TF, Gibney E, Igoe F, Gordon MK, Fitch JM, Fessler LI, Birk DE (1993) Type V collagen: molecular structure and fibrillar organization of the chicken alpha 1(V) NH2-terminal domain, a putative regulator of corneal fibrillogenesis. J Cell Biol 121:1181–1189CrossRefPubMedGoogle Scholar
  35. Mahoney ZX, Stappenbeck TS, Miner JH (2008) Laminin {alpha}5 influences the architecture of the mouse small intestine mucosa. J Cell Sci 121:2493–2502CrossRefPubMedGoogle Scholar
  36. Mao Y, Schwarzbauer JE (2005) Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol 24:389–399CrossRefPubMedGoogle Scholar
  37. Marneros AG, Olsen BR (2005) Physiological role of collagen XVIII and endostatin. FASEB J 19:716–728CrossRefPubMedGoogle Scholar
  38. McMillan JR, Akiyama M, Shimizu H (2003) Epidermal basement membrane zone components: ultrastructural distribution and molecular interactions. J Dermatol Sci 31:169–177CrossRefPubMedGoogle Scholar
  39. Mecham R (1999) Elastin. In: Kreis T, Vale R (eds) Guidebook to the extracellular matrix, anchor, and adhesion proteins. Oxford University Press, New York, pp 414–417Google Scholar
  40. Metcalfe K, Rucka AK, Smoot L, Hofstadler G, Tuzler G, McKeown P, Siu V, Rauch A, Dean J, Dennis N, Ellis I, Reardon W, Cytrynbaum C, Osborne L, Yates JR, Read AP, Donnai D, Tassabehji M (2000) Elastin: mutational spectrum in supravalvular aortic stenosis. Eur J Hum Genet 8:955–963CrossRefPubMedGoogle Scholar
  41. Miner JH, Sanes JR (1996) Molecular and functional defects in kidneys of mice lacking collagen α3(IV): implications for Alport syndrome. J Cell Biol 135:1403–1413CrossRefPubMedGoogle Scholar
  42. Miner JH, Yurchenco PD (2004) Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol 20:255–284CrossRefPubMedGoogle Scholar
  43. Mullins RF, Olvera MA, Clark AF, Stone EM (2007) Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration. Exp Eye Res 84:378–380CrossRefPubMedGoogle Scholar
  44. Murshed M, Smyth N, Miosge N, Karolat J, Krieg T, Paulsson M, Nischt R (2000) The absence of nidogen 1 does not affect murine basement membrane formation. Mol Cell Biol 20:7007–7012CrossRefPubMedGoogle Scholar
  45. Ninomiya Y, Kagawa M, Iyama K, Naito I, Kishiro Y, Seyer JM, Sugimoto M, Oohashi T, Sado Y (1995) Differential expression of two basement membrane collagen genes, COL4A6 and COL4A5, demonstrated by immunofluorescence staining using peptide-specific monoclonal antibodies. J Cell Biol 130:1219–1229CrossRefPubMedGoogle Scholar
  46. Olsen BR, Ninomiya Y (1999a) Collagens: overview of the family. In: Kreis T, Vale R (eds) Guidebook to the extracellular matrix, anchor, and adhesion proteins. Oxford University Press, New York, pp 380–383Google Scholar
  47. Olsen BR, Ninomiya Y (1999b) Fibrillar collagens. In: Kreis T, Vale R (eds) Guidebook to the extracellular matrix, anchor, and adhesion proteins. Oxford University Press, New York, pp 383–387Google Scholar
  48. Ortiz-Urda S, Garcia J, Green CL, Chen L, Lin Q, Veitch DP, Sakai LY, Lee H, Marinkovich MP, Khavari PA (2005) Type VII collagen is required for Ras-driven human epidermal tumorigenesis. Science 307:1773–1776CrossRefPubMedGoogle Scholar
  49. Park ES, Putnam EA, Chitayat D, Child A, Milewicz DM (1998) Clustering of FBN2 mutations in patients with congenital contractural arachnodactyly indicates an important role of the domains encoded by exons 24 through 34 during human development. Am J Med Genet 78:350–355CrossRefPubMedGoogle Scholar
  50. Peterkofsky B (1991) Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr 54:1135S–1140SPubMedGoogle Scholar
  51. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, Marro B, Desmettre T, Cohen SY, Roullet E, Dracon M, Fardeau M, Van Agtmael T, Kerjaschki D, Antignac C, Ronco P (2007) COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med 357:2687–2695CrossRefPubMedGoogle Scholar
  52. Rahn DD, Acevedo JF, Roshanravan S, Keller PW, Davis EC, Marmorstein LY, Word RA (2009) Failure of pelvic organ support in mice deficient in fibulin-3. Am J Pathol 174:206–215CrossRefPubMedGoogle Scholar
  53. Ramirez F, Dietz HC (2007) Marfan syndrome: from molecular pathogenesis to clinical treatment. Curr Opin Genet Dev 17:252–258CrossRefPubMedGoogle Scholar
  54. Ramirez F, Sakai LY, Rifkin DB, Dietz HC (2007) Extracellular microfibrils in development and disease. Cell Mol Life Sci 64:2437–2446CrossRefPubMedGoogle Scholar
  55. Rattenholl A, Pappano WN, Koch M, Keene DR, Kadler KE, Sasaki T, Timpl R, Burgeson RE, Greenspan DS, Bruckner-Tuderman L (2002) Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen. J Biol Chem 277:26372–26378CrossRefPubMedGoogle Scholar
  56. Ricard-Blum S, Ruggiero F (2005) The collagen superfamily: from the extracellular matrix to the cell membrane. Pathol Biol (Paris) 53:430–442Google Scholar
  57. Robins SP (2007) Biochemistry and functional significance of collagen cross-linking. Biochem Soc Trans 35:849–852CrossRefPubMedGoogle Scholar
  58. Sakai T, Johnson KJ, Murozono M, Sakai K, Magnuson MA, Wieloch T, Cronberg T, Isshiki A, Erickson HP, Fassler R (2001) Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis. Nat Med 7:324–330CrossRefPubMedGoogle Scholar
  59. Sanes JR, Apel ED, Gautam M, Glass D, Grady RM, Martin PT, Nichol MC, Yancopoulos GD (1998) Agrin receptors at the skeletal neuromuscular junction. Ann N Y Acad Sci 841:1–13CrossRefPubMedGoogle Scholar
  60. Shaw LM, Olsen BR (1991) FACIT collagens: diverse molecular bridges in extracellular matrices. Trends Biochem Sci 16:191–194CrossRefPubMedGoogle Scholar
  61. Shifren A, Mecham RP (2006) The stumbling block in lung repair of emphysema: elastic fiber assembly. Proc Am Thorac Soc 3:428–433CrossRefPubMedGoogle Scholar
  62. Smyth N, Vatansever HS, Murray P, Meyer M, Frie C, Paulsson M, Edgar D (1999) Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation. J Cell Biol 144:151–160CrossRefPubMedGoogle Scholar
  63. Timpl R (1989) Structure and biological activity of basement membrane proteins. Eur J Biochem 180:487–502CrossRefPubMedGoogle Scholar
  64. Varga J, Pasche B (2008) Antitransforming growth factor-beta therapy in fibrosis: recent progress and implications for systemic sclerosis. Curr Opin Rheumatol 20:720–728CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Renal DivisionWashington University School of MedicineSt. LouisUSA

Personalised recommendations