Abstract
A glycoslylated sulfate-containing protein known as myelin-associated glycoprotein (MAG) appears to be unique to the central and peripheral nervous systems. This component has been characterized and cDNA clones have been isolated.
MAG is a member of the immunoglobulin superfamily. The principal form of MAG synthesized in brain during active myelination has an apparent molecular weight of 100,000. Alternate exon splicing leads to an additional 5000-dalton smaller form with a different C terminus.
In patients with multiple sclerosis, MAG is rapidly lost in areas of active disease. It is immunologically reactive in patients with benign monoclonal gammopathy associated with peripheral neuropathy.
The role of MAG in the formation of the myelin sheath and its participation in autoimmune neurological disorders are outlined.
Key words: myelin-associated glycoprotein, cell adhesion molecules, cDNA clones, immunoglobulin superfamily, sulfated glucuronic acid, paraproteinemias, peripheral neuropathy, gangliosides
References
- Arquint, M., Roder, J., Chia, L.-S., Down, J., Wilkinson, D., Bayley, H., Braun, P., and Dunn, R. (1987). Molecular cloning and primary structure of myelin-associated glycoprotein.Proc. Natl. Acad. Sci. USA84600–604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brady, R. O., and Quarles, R. H. (1973). The enzymology of myelination.Mol. Cell. Biochem.223–29. [DOI] [PubMed] [Google Scholar]
- Braun, P. E., Frail, D. E., and Latov, N. (1982). Myelin-associated glycoprotein is the antigen for a monoclonal IgM in polyneuropathy.J. Neurochem.391261–1265. [DOI] [PubMed] [Google Scholar]
- Chou, K. H., Ilyas, A. A. Evans, J. E., Quarles, R. H., and Jungalwala, F. B. (1985). Structure of a glycolipid reacting with monoclonal IgM in neuropathy and with KNN-1.Biochem. Biophys. Res. Commun.128383–388. [DOI] [PubMed] [Google Scholar]
- Chou, K. H., Ilyas, A. A., Evans, J. E., Costello, C., Quarles, R. H., and Jungalwala, F. B. (1986). Structure of sulfated glucuronyl glycolipids in the nervous system reacting with HNK-1 antibody and some IgM paraproteins in neuropathy.J. Biol. Chem.26111717–11725. [PubMed] [Google Scholar]
- Dobersen, M. J., Hammer, J. A., Noronha, A. B., MacIntosh, T. D., Trapp, B. D., Brady, R. O., and Quarles, R. H. (1985a). Generation and characterization of mouse monoclonal antibodies to the myelin-associated glycoprotein (MAG).Neurochem. Res.10499–513. [DOI] [PubMed] [Google Scholar]
- Dobersen, M. J., Gascon, P., Trost, S., Hammer, J. A., Goodman, S., Noronha, A. B., O'Shannessy, D. J., Brady, R. O., and Quarles, R. H. (1985b). Murine monoclonal antibodies to the myelin-associated glycoprotein react with large granular lympocytes of human blood.Proc. Natl. Acad. Sci. USA82552–555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Everly, J. L., Brady, R. O., and Quarles, R. H. (1973). Evidence that the major protein in rat sciatic nerve myelin is a glycoprotein.J. Neurochem.21329–334. [DOI] [PubMed] [Google Scholar]
- Figlewicz, D. A., Quarles, R. H., Johnson, D., Barbarash, G. R., and Sternberger, N. H. (1981). Biochemical demonstration of the myelin-associated glyocoprotein in the peripheral nervous system.J. Neurochem.37749–758. [DOI] [PubMed] [Google Scholar]
- Frail, D. E., and Braun, P. E. (1985). Developmental expression of the myelin-associated glycoprotein in the central nervous system of dysmyelinating mutant mice.J. Neurochem.451071–1075. [DOI] [PubMed] [Google Scholar]
- Gregson, N. A., and Leibowitz, S. (1985). IgM paraproteinemia, polyneuropathy and myelinassociated glycoprotein.J. Neuropathol. Appl. Neurobiol.11329–347. [DOI] [PubMed] [Google Scholar]
- Hays, A. P., Latov, N., Takatsu, M., and Sherman, W. H. (1987). Experimental demyelination of nerve induced by serum of patients with neuropathy and an anti-MAG IgM M-protein.Neurology37242–256. [DOI] [PubMed] [Google Scholar]
- Ilyas, A. A., Quarles, R. H., MacIntosh, T. D., Dobersen, M. J., Trapp, B. D., Dalackas, M. C., and Brady, R. O. (1984). IgM in a human neuropathy related to paraproteinemia binds to a carbohydrate determinant in the myelin-associated glycoprotein and to a ganglioside.Proc. Natl. Acad. Sci. USA811225–1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ilyas, A. A., Quarles, R. H., Dalakas, M. C., and Brady, R. O. (1985a). Polyneuropathy with monoclonal gammopathy: Glycolipids are frequently antigens for IgM paraproteins.Proc. Natl. Acad. Sci. USA826697–6700. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ilyas, A. A. Quarles, R. H., Dalakas, M. C., Fishman, P. H., and Brady, R. O. (1985b). Monoclonal IgM in a patient with paraproteinemic polyneuropathy binds to gangliosides containing disialosly groups.Ann. Neurol.18655–659. [DOI] [PubMed] [Google Scholar]
- Ilyas, A. A., Delakas, M. C., Brady, R. O., and Quarles, R. H. (1986). Sulfated glucuronyl glycolipids reacting with anti-myelin-associated glycoprotein monoclonal antibodies including IgM paraproteins in neuropathy: Species distribution and partial characterization of epitopes.Brain Res.3851–9. [DOI] [PubMed] [Google Scholar]
- Inuzuka, T., Johnson, D., and Quarles, R. H. (1987). Myelin-associated glycoprotein in the central and peripheral nervous system of quaking mice.J. Neurochem.49597–602. [DOI] [PubMed] [Google Scholar]
- Itoyama, Y., Sternberger, N. H., Webster, H. deF., Quarles, R. H., Cohen, S. R., and Richardson, E. P., Jr. (1980). Immunocytochemical observations on the distribution of the myelin-associated glycoprotein and myelin basic protein in multiple sclerosis lesions.Ann. Neurol.7167–177. [DOI] [PubMed] [Google Scholar]
- Johnson, D., Sato, S., Quarles, R. H., Inuzuka, T., Brady, R. O., and Tourtellotte, W. W. (1986a). Quantitation of the myelin-associated glycoprotein in human nervous tissue from controls and multiple sclerosis patients.J. Neurochem.461086–1093. [DOI] [PubMed] [Google Scholar]
- Johnson, D., Hafler, D. A., Fallis, R. J., Lees, M. B., Brady, R. O., Quarles, R. H., and Weiner, H. L. (1986b). Cell-mediated immunity to myelin-associated glycoprotein, proteolipid protein, and myelin basic protein in multiple sclerosis.J. Neuroimmunol.13 99–108. [DOI] [PubMed] [Google Scholar]
- Lai, C., Brow, M. A., Nave, K.-A., Noronha, A. B., Quarles, R. H., Bloom, F. E., Milner, R. J., and Sutcliff, J. G. (1987). Two forms of 1B236 myelin-associated glycoprotein, a cell adhesion molecule for postnatal neural development, are produced by alternative splicing.Proc. Natl. Acad. Sci. USA844337–4341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matthieu, J.-M., Brady, R. O., and Quarles, R. H. (1974a). Anomalies of myelin-associated glycoprotein in quaking mice.J. Neurochem.22291–296. [DOI] [PubMed] [Google Scholar]
- Matthieu, J.-M., Quarles, R. H., Webster, H. deF., Hogan, E. L., and Brady, R. O. (1974b). Characterization of the fraction obtained from the CNS of Jimpy mice by a procedure for myelin isolation.J. Neurochem.23517–523. [DOI] [PubMed] [Google Scholar]
- Matthieu, J.-M., Quarles, R. H., Poduslo, J. F., and Brady, R. O. (1975a). [35]S-Sulfate incorporation into myelin glycoproteins. I. Central nervous system.Biochim. Biophys. Acta.392159–166. [DOI] [PubMed] [Google Scholar]
- Matthieu, J.-M., Everly, J. L., Brady, R. O., and Quarles, R. H. (1975b). [35S]Sulfate incorporation into myelin glycoproteins. II. Peripheral nervous tissue.Biochim. Biophys. Acta392167–174. [DOI] [PubMed] [Google Scholar]
- McGarry, R. C., Helfand, S. L., Quarles, R. H., and Roder, J. C. (1983). Recognition of myelin-associated glycoprotein by the monoclonal antibody HNK-1.Nature306376–378. [DOI] [PubMed] [Google Scholar]
- Mendell, J. R., Sahenk, Z., Whitaker, J. N., Trapp, B. D., Yates, A. J., Griggs, R. C., and Quarles, R. H. (1985). Polyneuropathy and IgM monoclonal gammopathy: Study on pathogenetic role of anti-MAG antibodies.Ann. Neurol.17243–254. [DOI] [PubMed] [Google Scholar]
- Moller, J. R., Yanagisawa, K., Brady, R. O., Tourtellotte, W. W., and Quarles, R. H. (1987). Myelin-associated glycoprotein in multiple sclerosis lesions: A quantitative and qualitative analysis.Ann. Neurol.21135–141. [DOI] [PubMed] [Google Scholar]
- Noronha, A. B., Harper, J. R., Ilyas, A. A., Reisfeld, R. A., and Quarles, R. H. (1986). Myelin-associated glycoprotein shares an antigenic determinant with a glycoprotein of human melanoma cells.J. Neurochem.471558–1565. [DOI] [PubMed] [Google Scholar]
- Quarles, R. H. (1983/1984). Myelin-associated glycoprotein in development and disease.Dev. Neurosci.6285–303. [DOI] [PubMed] [Google Scholar]
- Quarles, R. H., and Brady, R. O. (1970). Sialoglycoproteins and several glycosidases in developing rat brain.J. Neurochem.17801–807. [DOI] [PubMed] [Google Scholar]
- Quarles, R. H., and Brady, R. O. (1971). Synthesis of glycoproteins and gangliosides in developing rat brain.J. Neurochem.181809–1820. [DOI] [PubMed] [Google Scholar]
- Quarles R. H., Everly, J. L., and Brady, R. O. (1972). Demonstration of a glycoprotein which is associated with a purified myelin fraction from rat brain.Biochem. Biophys. Res. Commun.47491–497. [DOI] [PubMed] [Google Scholar]
- Quarles, R. H., Everly, J. L., and Brady, R. O. (1973). Myelin-associated glycoprotein: A developmental change.Brain Res.58506–509. [DOI] [PubMed] [Google Scholar]
- Quarles, R. H., Johnson, D., Brady, R. O., and Sternberger, N. H. (1981). Preparation and characterization of antisera to the myelin-associated glycoprotein.Neurochem. Res.61115–1127. [DOI] [PubMed] [Google Scholar]
- Quarles, R. H., Ilyas, A. A., and Willison, H. J. (1986). Antibodies to glycolipids in demyelinating diseases of the human peripheral nervous system.Chem. Phys. Lipids42235–248. [DOI] [PubMed] [Google Scholar]
- Rouslahti, E., and Pierschbacher, M. D. (1986). Arg-Gly-Asp: A versatile cell recognition signal.Cell44517–518. [DOI] [PubMed] [Google Scholar]
- Saito, T., Sherman, W. L., and Latov, N. (1983). Specificity and idiotype of M-proteins that react with MAG in patients with peripheral neuropathy.J. Immunol.1302496–2498. [PubMed] [Google Scholar]
- Salzer, J. L., Holmes, W. P., and Colman, D. R. (1987). The amino acid sequences of the myelin-associated glycoproteins: Homology to the immunoglobulin gene superfamily.J. Cell Biol.104957–965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sato, S., Quarles, R. H., and Brady, R. O. (1982). Susceptibility of the myelin-associated glycoprotein and basic protein to a neutral protease in highly purified myelin from human and rat brain.J. Neurochem.3997–105. [DOI] [PubMed] [Google Scholar]
- Sato, S., Quarles, R. H., Brady, R. O., and Tourtellotte, W. W. (1984). Elevated neutral protease activity in myelin from brains of patients with multiple sclerosis.Ann. Neurol.15264–267. [DOI] [PubMed] [Google Scholar]
- Steck, A., Murray, N., Meier, C., Page, N., and Perruisseau, G. (1983). Demyelinating neuropathy and monoclonal IgM antibody to myelin-associated glycoprotein.Neurology3319–23. [DOI] [PubMed] [Google Scholar]
- Sternberger, N. H., Quarles, R. H., Itoyama, Y., and Webster, H. deF. (1979). Myelin-associated glycoprotein demonstrated immunocytochemically in myelin and myelin-forming cells of developing rat.Proc. Natl. Acad. Sci. USA761510–1514. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sutcliffe, J. G., Milner, R. J., Shinnick, T. M., and Bloom, F. E. (1983). Identifying the protein products of brain-specific genes with antibodies to chemically synthesized peptides.Cell33671–682. [DOI] [PubMed] [Google Scholar]
- Takatsu, M., Hays, A., Latov, N., Abrahams, G. W., Nemni, R., Sherman, W. H., Nobile-Orazio, E., Saito, T., and Freddo, L. (1985). Immunofluorescence study of patients with neuropathy and IgM M protein.Ann. Neurol.18173–181. [DOI] [PubMed] [Google Scholar]
- Trapp, B. D., Quarles, R. H., and Suzuki, K. (1984). Immunocytochemical studies of Quaking mice support a role for the myelin-associated glycoprotein in forming and maintaining the perioaxonal space and periaxonal cytoplasmic collar of myelinating Schwann cells.J. Cell Biol.99595–606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wagjt, A., and Gorny, M. (1983). CSF antibodies to myelin basic protein and to myelin-associated glycoprotein in multiple sclerosis.Acta Neurol. Scand.68337–343. [DOI] [PubMed] [Google Scholar]
- Willison, H. J., Minna, J. D., Brady, R. O., and Quarles, R. H. (1986). Glycoconjugates in nervous tissue and small cell lung cancer share immunologically cross-reactive carbohydrate determinants.J. Neuroimmunol.10353–365. [DOI] [PubMed] [Google Scholar]
- Yanagisawa, K., and Quarles, R. H. (1986). Jimpy mice: Quantitation of myelin-associated glycoprotein and other proteins.J. Neurochem.47322–325. [DOI] [PubMed] [Google Scholar]
- Yanagisawa, K., Quarles, R. H., Johnson, D., Brady, R. O., and Whitaker, J. N. (1985). A derivative of myelin-associated glycoprotein (dMAG) in cerebrospinal fluid of normals and patients with neurological disease.Ann. Neurol.18464–469. [DOI] [PubMed] [Google Scholar]
