Abstract
Calcium concentrations in the extracellular space are 4 to 5 orders of magnitude larger than inside cells. These concentrations are highly controlled by a unique receptor system (Brown et al., 1995); Ward and Ricardi, this book; Brown et al., this book). Free calcium concentration in serum has been determined to be 1.2 mM, however, spatial and time-dependent fluctuations have been detected (for a review, see Maurer et al., 1996). Many different proteins in the extracellular space bind calcium ions and a variety of calcium-binding motifs have been identified in these proteins, e.g. the EF-hand motif, which is common in cytosolic proteins (Maurer et al., 1996). Calcium ions bound to extracellular proteins may serve various functions, but primarily stabilize protein structure which explains tight calcium binding (micromolar or smaller K D values). In addition, sites for weakly bound calcium ions may sense variations in extracellular calcium levels and may be involved in regulation (Maurer et al., 1996); (Koch et al., 1997). This chapter will focus on relevant findings concerning functional and pathological effects of calcium binding to two extracellular matrix proteins (fibrillin-1 and COMP) and the cell adhesion protein E-cadherin. Possible molecular mechanisms for these effects will be discussed as well.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ashworth, J.L., Murphy, G., Rock, M.J., Sherratt, M.J., Shapiro, S.D., Shuttleworth, C.A. and Kielty, C.M., 1999, Fibrillin degradation by matrix metalloproteinases: Implications for connective tissue remodelling, Biochem. J. 340, 171–181.
Becker, K.F., Atkinson, M.J., Reich, U., Becker, I., Nekarda, H., Siewert, J.R. and Hofler, H., 1994, E-cadherin gene mutations provide clues to diffuse type gastric carcinomas, Cancer Res. 54, 3845–3852.
Briggs, M.D., Hoffman, S.M., King, L.M., Olsen, A.S., Mohrenweiser, H., Leroy, J.G., Mortier, G.R., Rimoin, D.L., Lachman, R.S., Gaines, E.S. et al., 1995, Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene, Nat. Genet. 10, 330–336.
Brown, E.M., Vassilev, RM. and Hebert, S.C., 1995, Calcium ions as extracellular messengers, Cell 83, 679–682.
Brown, E.M., Pollak, M. and Hebert, S.C., 1998, The extracellular calcium-sensing receptor: Its role in health and disease, Annu. Rev. Med. 49, 15–29.
Deere, M., Sanford, T., Francomano, C.A., Daniels, K. and Hecht, J.T., 1999, Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia, Am. J. Med. Genet. 85, 486–490.
Delot, E., Brodie, S.G., King, L.M., Wilcox, W.R. and Cohn, D.H., 1998, Physiological and pathological secretion of cartilage oligomeric matrix protein by cells in culture, J. Biol. Chem. 273, 26692–26697.
Delot, E., King, L.M., Briggs, M.D., Wilcox, W.R. and Cohn, D.H., 1999, Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene, Hum. Mol. Genet. 8, 123–128.
DiCesare, P., Hauser, N., Lehman, D., Pasumarti, S. and Paulsson, M., 1994, Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon, FEBS Lett. 354, 237–240.
DiCesare, P., Carlson, C., Stollerman, E., Chen, F., Leslie, M. and Perris, R., 1997, Expression of cartilage oligomeric matrix protein by human synovium, FEBS Lett. 412, 249–252.
Downing, A.K., Knott, V., Werner, J.M., Cardy, CM., Campbell, I.D. and Handford, P.A., 1996, Solution structure of a pair of calcium-binding epidermal growth factor-like domains: Implications for the Marfan syndrome and other genetic disorders, Cell 85, 597–605.
Forslind, K., Eberhardt, K., Jonsson, A. and Saxne, T., 1992, Increased serum concentrations of cartilage oligomeric matrix protein. A prognostic marker in early rheumatoid arthritis, Br. J. Rheumatol 3, 593–598.
Guilford, P., Hopkins, J., Harraway, J., McLeod, M., McLeod, N., Harawira, P., Taite, H., Scoular, R., Miller, A. and Reeve, A.E., 1998, E-cadherin germline mutations in familial gastric cancer, Nature 392, 402–405.
Handford, P., Downing, A.K., Rao, Z., Hewett, D.R., Sykes, B.C. and Kielty, C.M., 1995, The calcium binding properties and molecular organization of epidermal growth factor-like domains in human fibrillin-1, J. Biol. Chem. 270, 6751–6756.
Hecht, J.T., Deere, M., Putnam, E., Cole, W., Vertel, B., Chen, H. and Lawler, J., 1998, Characterization of cartilage oligomeric matrix protein (COMP) in human normal and pseudoachondroplasia musculoskeletal tissues, Matrix Biol. 17, 269–278.
Hecht, J.T., Nelson, L.D., Crowder, E., Wang, Y., Elder, F.F., Harrison, W.R., Francomano, C.A., Prange, C.K., Lennon, G.G., Deere, M., et al., 1995, Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia, Nat. Genet. 10, 325–329.
Hedbom, E., Antonsson, P., Hjerpe, A., Aeschlimann, D., Paulsson, M., Rosa-Pimentel, E., Sommarin, Y., Wendel, M., Oldberg, A. and Heinegard, D., 1992, Cartilage matrix proteins. An acidic oligomeric protein (COMP) detected only in cartilage, J. Biol. Chem. 267, 6132–6136.
Hermiston, M.L. and Gordon, J.I., 1995, Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin, Science 270, 1203–1207.
Hyafil, F., Morello, D., Babinet, C. and Jacob, F., 1980, A cell surface glycoprotein involved in the compaction of embryonal carcinoma cells and cleavage stage embryos, Cell 21, 927–934.
Hyafil, F., Babinet, C. and Jacob, F., 1981, Cell-cell interactions in early embryogenesis: A molecular approach to the role of calcium, Cell 26, 447–454.
International Working Group on Constitutional Diseases of Bone, 1998, International no-menclature and classification of the osteochondrodysplasias, 1997, International Working Group on Constitutional Diseases of Bone, Am. J. Med. Genet. 79, 376–382.
Karayiannakis, A.J., Syrigos, K.N., Efstathiou, J., Valizadeh, A., Noda, M., Playford, R.J., Kmiot, W. and Pignatelli, M., 1998, Expression of catenins and E-cadherin during epithelial restitution in inflammatory bowel disease, J. Pathol. 185, 413–418.
Knott, V., Downing, A.K., Cardy, C.M. and Handford, P., 1996, Calcium binding properties of an epidermal growth factor-like domain pair from human fibrillin-1, J. Mol. Biol. 255, 22–27.
Koch, A.W., Pokutta, S., Lustig, A. and Engel, J., 1997, Calcium binding and homoassociation of E-cadherin domains, Biochemistry 36, 7697–7705.
Koch, A.W., Bozic, D., Pertz, O. and Engel, J., 1999, Homophilic adhesion by Cadherins, Curr. Opin. Struct. Biol. 9, 275–281.
Kraulis, P.J., 1991, MOLSCRIPT, a program to produce both detailed and schematic plots of protein structure, J. Appl. Cryst. 24, 946–950.
Maddox, B.K., Keene, D.R., Sakai, L.Y., Charbonneau, N.L., Morris, N.P., Ridgway, C.C., Boswell, B.A., Sussman, M.D., Horton, W.A., Bachinger, H.P. and Hecht, J.T., 1997, The fate of cartilage oligomeric matrix protein is determined by the cell type in the case of a novel mutation in pseudoachondroplasia, J. Biol. Chem. 272, 30993–30997.
Malashkevich, V., Kammerer, R., Efimov, V., Schulthess, T. and Engel, J., 1996, The crystal structure of a five-stranded coiled coil in COMP: A prototype ion channel?, Science 274, 761–765.
Marra, A. and Isberg, R.R., 1996, Bacterial pathogenesis: Common entry mechanisms, Curr. Biol. 6, 1084–1086.
Maurer, P., Hohenester, E. and Engel, J., 1996, Extracellular calcium binding proteins, Curr. Opin. Cell Biol. 8, 609–617.
Maynard, J.A., Cooper, R.R. and Ponseti, I.V., 1972, A unique rough surfaced endoplasmic reticulum inclusion in pseudoachondroplasia, Lab. Invest. 26, 40–44.
Misenheimer, T.M. and Mosher, D.F., 1995, Calcium ion binding to thrombospondin 1, J. Biol. Chem. 270, 1729–1733.
Mörgelin, M., Heinegard, D., Engel, J. and Paulsson, M., 1992, Electron microscopy of native cartilage oligomeric matrix protein purified from the Swarm rat chondrosarcoma reveals a five-armed structure, J. Biol. Chem. 267, 6137–6141.
Nagar, B., Overduin, M., Ikura, M. and Rini, J.M., 1996, Structural basis of calcium-induced E-cadherin rigidification and dimerization, Nature 380, 360–364.
Neidhart, M., Hauser, N., Paulsson, M., Di Cesare, P.E., Michel, B.A. and Hauselmann, H.J., 1997, Small fragments of cartilage oligomeric matrix protein in synovial fluid and serum as markers for cartilage degradation, Br. J. Rheumatol. 36, 1151–1160.
Nose, A., Tsuji, K. and Takeichi, M., 1990, Localization of specificity determining sites in Cadherin cell adhesion molecules, Cell 6, 147–155.
Oldberg, A., Antonsson, P., Lindblom, K. and Heinegard, D., 1992, COMP (cartilage oligomeric matrix protein) is structurally related to the thrombospondins, J. Biol. Chem. 267, 22346–22350.
Perl, A.K., Wilgenbus, P., Dahl, U., Semb, H. and Christofori, G., 1998, A causal role for E-cadherin in the transition from adenoma to carcinoma, Nature 392, 190–193.
Persson, E., Selander, M., Linse, S., Drakenberg, T., Oehlin, A.-K. and Stenflo, J., 1989. Calcium binding to the isolated β-hydroxyaspartic acid-containing epidermal growth factor-like domain of bovine factor X, J. Biol. Chem. 264, 16897–16904.
Pertz, O., Bozic, D., Koch, A.W., Fauser, C., Brancaccio, A. and Engel, J., 1999, A new crystal structure Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation, EMBO J. 18, 1738–1747.
Pokutta, S., Herrenknecht, K., Kemler, R. and Engel, J., 1994, Conformational changes of the recombinant extracellular domain of E-cadherin upon calcium binding, Eur. J. Biochem. 223, 1019–1026.
Ramirez, F. and Pereira, L., 1999, The fibrillins, Int. J. Biochem. Cell. Biol. 31, 255–259.
Rand, M.D., Lindblom, A., Carlson, J., Villoutreix, B.O. and Stenflo, J., 1997, Calcium binding to tandem repeats of EGF-like modules. Expression and characterization of the EGF-like modules of human Notch-1 implicated in receptor-ligand interactions, Protein Sci. 6, 2059–2071.
Reinhardt, D.P., Ono, R.N. and Sakai, L.Y., 1997, Calcium stabilizes fibrillin-1 against proteolytic degradation, J. Biol. Chem. 272, 1231–1236.
Reinhardt, D.P., Ono, R.N., Notbohm, H., Mueller, P.K., Bächinger, H.P. and Sakai, L.Y., 2000, Mutations in calcium-binding EGF modules render fibrillin-1 susceptible to proteolysis: A potential disease-causing mechanism in Marfan syndrom, J. Biol. Chem. 275, 12339–12345.
Ringwald, M., Schuh, R., Vestweber, D., Eistetter, H., Lottspeich, F., Engel, J., Dolz, R., Jahnig, F., Epplen, J., Mayer, S., Müller, C. and Kemler, R., 1987, The structure of cell adhesion molecule uvomorulin. Insights into the molecular mechanism of Ca2+-dependent cell adhesion, EMBO J. 6, 3647–3653.
Sakai, L.Y. and Keene, D.R., 1994, Fibrillin: Monomers and microfibrils, Methods Enzymol. 245, 29–52.
Sansonetti, P.J., Mounier, J., Prévost, M.C. and Mege, R.M., 1994, Cadherin expression is required for the spread of Shigella flexneri between epithelial cells, Cell 76, 829–839.
Saxne, T. and Heinegard, D., 1992, Cartilage oligomeric matrix protein: A novel marker of cartilage turnover detectable in synovial fluid and blood, Br. J. Rheumatol. 31, 583–591.
Semb, H. and Christofori, G., 1998, The tumor-suppressor function of E-cadherin, Am. J. Hum. Genet. 63, 1588–1593.
Shapiro, L., Fannon, A.M., Kwong, P.D., Thompson, A., Lehmann, M.S., Grubel, G., Legrand, J.F., Als-Nielsen, J., Colman, D.R. and Hendrickson, W.A., 1995, Structural basis of cell-cell adhesion by Cadherins, Nature 374, 327–337.
Smallridge, R.S., Whiteman, P., Doering, K., Handford, P.A. and Downing, A.K., 1999, EGF-like domain calcium affinity modulated by N-terminal domain linkage in human fibrillin-1, J. Mol. Biol 286, 661–668.
Takeichi, M., 1988, The Cadherins: Cell-cell adhesion molecules controlling animal morphogenesis, Development 102, 639–655.
Tamura, K., Shan, W.-S., Hendrickson, W.A., Colman, D.R. and Shapiro, L., 1998, Structure-function analysis of cell adhesion by neural (N-) Cadherin, Neuron 20, 1153–1163.
Vestweber, D. and Kemler, R., 1984, Rabbit antiserum against a purified surface glycoprotein decompacts mouse preimplantation embryos and reacts with specific adult tissues, Exp. Cell. Res. 52, 169–178.
Wu, Q. and Maniatis, T., 1999, A striking organization of a large family of human neural cadherin-like cell adhesion genes, Cell 97, 779–790.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer Science+Business Media New York
About this chapter
Cite this chapter
Koch, A.W., Engel, J., Maurer, P. (2000). Calcium Binding to Extracellular Matrix Proteins, Functional and Pathological Effects. In: Pochet, R., Donato, R., Haiech, J., Heizmann, C., Gerke, V. (eds) Calcium: The Molecular Basis of Calcium Action in Biology and Medicine. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0688-0_9
Download citation
DOI: https://doi.org/10.1007/978-94-010-0688-0_9
Publisher Name: Springer, Dordrecht
Print ISBN: 978-0-7923-6422-1
Online ISBN: 978-94-010-0688-0
eBook Packages: Springer Book Archive