Reduced Glycosaminoglycan Sulfation Diminishes the Agrin Signal Transduction PathwayMcDonnell K.M.W. · Grow W.A.
Department of Anatomy, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Ariz., USA
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Article / Publication Details
Proteoglycans consist of a protein core complexed to glycosaminoglycan (GAG) side chains, are abundant in skeletal muscle cell membranes and basal lamina, and have important functions in neuromuscular synapse development. Treatment with chlorate results in the undersulfation of heparan sulfate and chondroitin sulfate GAGs in cell culture. In addition, chlorate treatment decreases the frequency of spontaneous acetylcholine receptor (AChR) clustering in skeletal muscle cell culture. AChRs and other molecules cluster to form the postsynaptic component of neuromuscular synapses. Chlorate treatment is shown here to decrease the frequency of agrin-induced AChR clustering and agrin-induced tyrosine phosphorylation of the AChR β-subunit. These data suggest that reduced GAG chain sulfation decreases the frequency of AChR clustering by diminishing the agrin signal transduction pathway.
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- Anderson MJ, Cohen MW (1977): Nerve-induced and spontaneous redistribution of acetylcholine receptors on cultured muscle cells. J Physiol (Lond) 268:757–773.
- Anderson MJ, Fambrough DM (1983]: Aggregates of acetylcholine receptors are associated with plaques of a basal lamina heparan sulfate proteoglycan on the surface of skeletal muscle fibers. J Cell Biol 97:1396–1422.
- Anderson MJ, Klier FG, Tanguay KE (1984): Acetylcholine receptor aggregation parallels the deposition of a basal lamina proteoglycan during development of the neuromuscular junction. J Cell Biol 99:1769–1784.
- Angello JC, Hauschka SD (1979): Hyaluronic acid synthesis and turnover by myotubes in culture. Dev Biol 73:322–337.
- Apel ED, Roberds SL, Campbell KP, Merlie JP (1995): Rapsyn may function as a link between the acetylcholine receptor and the agrin-binding dystrophin-associated glycoprotein complex. Neuron 15:115–126.
- Baeuerle, PA, Huttner WB (1986): Chlorate – A potent inhibitor of protein sulfation in intact cells. Biochem Biophys Res Commun 141:870–877.
- Bayne EK, Anderson MJ, Fambrough DM (1984): Extracellular matrix organization in developing muscle: Correlation with acetylcholine receptor aggregates. J Cell Biol 99:1486–1501.
- Blau HM, Pavlath GK, Hardeman EC, Chiu CP, Silberstein L, Webster SG, Miller SC, Webster C (1985): Plasticity of the differentiated state. Science 230:758–766.
- Bloch RJ (1983): Acetylcholine receptor clustering in rat myotubes: requirement for Ca2+ and effects of drugs which depolymerize microtubules. J Neurosci 3:2670–2680.
- Bowen DC, Park JS, Bodine S, Stark JL, Valenzuela DM, Stitt TN, Yancopoulos GD, Lindsay RM, Glass DJ, DiStefano PS (1998): Localization and regulation of MuSK at the neuromuscular junction. Dev Biol 199:309–319.
- Brauer PR, Keller KM, Keller JM (1990): Concurrent reduction in the sulfation of heparan sulfate and basement membrane assembly in a cell model system. Development 110:805–813.
- Campanelli JT, Gayer GG, Scheller RH (1996): Alternative RNA splicing that determines agrin activity regulates binding to heparin and α-dystroglycan. Development 122:1663–1672.
- Campanelli JT, Roberds SL, Campbell KP, Scheller RH (1994): A Role for dystrophin-associated glycoproteins and utrophin in agrin-induced AChR clustering. Cell 77:663–674.
- Campbell KP (1995): Three muscular dystrophies: Loss of cytoskeleton-extracellular matrix linkage. Cell 80:675–679.
- Carrino DA, Caplan AI (1982): Isolation and preliminary characterization of proteoglycans synthesized by skeletal muscle. J Biol Chem 257:14145–14154.
- Carrino DA, Caplan AI (1984): Isolation and partial characterization of high-buoyant-density proteoglycans synthesized in ovo by embryonic chick skeletal muscle and heart. J Biol Chem 259:12419–12430.
- Cohen MW, Jacobson C, Godfrey EW, Campbell KP, Carbonetto S (1995): Distribution of alpha-dystroglycan during embryonic nerve-muscle synaptogenesis. J Cell Biol 129:1093–1101.
- DeChiara TM, Bowen DC, Valenzuela DM, Simmons MV, Poueymirou WT, Thomas S, Kinetz E, Compton DL, Rojas E, Park JS, Smith C, DiStefano PS, Glass DJ, Burden SJ, Yancopoulos GD (1996): The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo. Cell 85:501–512.
- Ervasti JM, Campbell KP (1993): A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin. J Cell Biol 122:809–823.
- Fambrough DM (1979): Control of acetylcholine receptors in skeletal muscle. Physiol Rev 59:165–227.
- Ferns MJ, Campanelli JT, Hoch W, Scheller RH, Hall ZW (1993): The ability of agrin to cluster AChRs depends on alternative splicing and on cell surface proteoglycans. Neuron 11:491–502.
- Ferns M, Deiner M, Hall ZW (1996): Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation. J Cell Biol 132:937–944.
- Fertuck HC, Salpeter MM (1976): Quantitation of junctional and extrajunctional acetylcholine receptors by electron microscope autoradiography after 125I-alpha-bungarotoxin binding at mouse neuromuscular junctions. J Cell Biol 69:144–158.
- Fischbach GD, Cohen SA (1973): The distribution of acetylcholine sensitivity over uninnervated and innervated muscle fibers grown in cell culture. Dev Biol 31:147–162.
- Fuhrer C, Sugiyama JE, Taylor RG, Hall ZW (1997): Association of muscle-specific kinase MuSK with the acetylcholine receptor in mammalian muscle. EMBO J 16:4951–4960.
- Gautam M, DeChiara TM, Glass DJ, Yancopoulos GD, Sanes JR (1999): Distinct phenotypes of mutant mice lacking agrin, MuSK, or rapsyn. Brain Res Dev Brain Res 114:171–178.
- Gesemann M, Cavalli V, Denzer AJ, Brancaccio A, Schumacher B, Ruegg MA (1996): Alternative splicing of agrin alters its binding to heparin, dystroglycan, and the putative agrin receptor. Neuron 16:755–767.
- Gesemann M, Denzer AJ, Ruegg MA (1995): Acetylcholine receptor-aggregating activity of agrin isoforms and mapping of the active site. J Cell Biol 128:625–636.
- Glass DJ, Bowen DC, Stitt TN, Radziejewski C, Bruno J, Ryan TE, Gies DR, Shah S, Mattsson K, Burden SJ, DeStefano PS, Valenzuela DM, DeChiara TM, Yancopolous GD (1996): Agrin acts via a MuSK receptor complex. Cell 85:513–523.
- Godfrey EW, Nitkin RM, Wallace BG, Rubin LL, McMahan UJ (1984): Components of Torpedo electric organ and muscle that cause aggregation of acetylcholine receptors on cultured muscle cells. J Cell Biol 99:615–627.
- Gordon H, Hall ZW (1989): Glycosaminoglycan variants in the C2 muscle cell line. Dev Biol 135:1–11.
- Gordon H, Lupa M, Bowen D, Hall Z (1993): A muscle cell variant defective in glycosaminoglycan biosynthesis forms nerve-induced but not spontaneous clusters of the acetylcholine receptor and the 43 kDa protein. J Neurosci 13:586–595.
- Graf RA, Kater SB, Gordon H (1999): Prolonged cytosolic calcium elevations in growth cones contacting muscle. Dev Neurosci 21:409–416.
- Greve H, Cully Z, Blumberg P, Kresse H (1988): Influence of chlorate on proteoglycan biosynthesis by cultured human fibroblasts. J Biol Chem 263:12886–12892.
- Grow WA, Ferns M, Gordon H (1999a): Agrin-independent activation of the agrin signal transduction pathway. J Neurobiol 40:356–365.
- Grow WA, Ferns M, Gordon H (1999b): A mechanism for AChR clustering distinct from agrin signaling. Dev Neurosci 21:436–443.
- Grow WA, Gordon H (2000a): Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signaling pathway. Eur J Neurosci 12:467–472.
- Grow WA, Gordon H (2000b): Sialic acid inhibits agrin signaling in C2 myotubes. Cell Tissue Res 299:273–279.
- Hirano Y, Kidokoro Y (1989): Heparin and heparan sulfate partially inhibit induction of acetylcholine receptor accumulation by nerve in Xenopus culture. J Neurosci 9:1555–1561.
- Hopf C, Hoch W (1997): Heparin inhibits acetylcholine receptor aggregation at two distinct steps in the agrin-induced pathway. Eur J Neurosci 9:1170–1177.
- Humphries DE, Silbert JE (1988): Chlorate: A reversible inhibitor of proteoglycan sulfation. Biochem Biophys Res Commun 154:365–371.
- Inestrosa NC, Miller JB, Silberstein L, Ziskind CL, Hall ZW (1983): Developmental regulation of 16S acetylcholinesterase and acetylcholine receptors in a mouse muscle cell line. Exp Cell Res 147:393–405.
- Jacobson C, Cote P, Rossi S, Rotundo R, Carbonetto S (2001): The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane. J Cell Biol 152:435–450.
- Johnson GD, Nogueira Araujo GM (1981): A simple method of reducing the fading of immunofluorescence during microscopy. J Immunol Methods 43:349–350.
- Kardami E, Spector D, Strohman RC (1988): Heparin inhibits skeletal muscle growth in vitro. Dev Biol 126:19–28.
- Keller KM, Brauer PR, Keller JM (1989): Modulation of cell surface heparan sulfate structure by growth of cells in the presence of chlorate. Biochemistry 28:8100–8107.
- Kujawa MJ, Pechak DG, Fiszman MY, Caplan AI (1986): Hyaluronic acid bonded to cell culture surfaces inhibits the program of myogenesis. Dev Biol 113:10–16.
- Marangi PA, Forsayeth JR, Mittaud P, Erb-Vogtli S, Blake DJ, Moransard M, Sander A, Fuhrer C (2001): Acetylcholine receptors are required for agrin-induced clustering of postsynaptic proteins. EMBO J 20:7060–7073.
- Marangi PA, Wieland ST, Fuhrer C (2002): Laminin-1 redistributes postsynaptic proteins and requires rapsyn, tyrosine phosphorylation, and Src and Fyn to stably cluster acetylcholine receptors. J Cell Biol 157:883–895.
- Martin GR, Kleinman HK, Terranova VP, Ledbetter S, Hassel JR (1984): The regulation of basement membrane formation and cell-matrix interactions by defined supramolecular complexes. Ciba Found Symp 108:197–212.
- Martin PT, Sanes JR (1995): Role for a synapse-specific carbohydrate in agrin-induced clustering of acetylcholine receptors. Neuron 14:743–754.
- Mayne R, Sanderson RD (1985): The extracellular matrix of skeletal muscle. Collagen Relat Res 5:449–468.
McMahan UJ (1990): The agrin hypothesis. Cold Spring Harbor Symp Quant Biol 50:407–418.
- Megeath LJ, Fallon JR (1998): Intracellular calcium regulates agrin-induced acetylcholine receptor clustering. J Neurosci 18:672–678.
- Miller RR, Rao JS, Festoff BW (1987): Proteoglycan synthesis by primary chick skeletal muscle during in vitro myogenesis. J Cell Physiol 133:258–266.
- Montanaro F, Gee SH, Jacobson C, Lindenbaum MH, Froehner SC, Carbonetto S (1998): Laminin and α-dystroglycan mediate acetylcholine receptor aggregation via a MuSK-independent pathway. J Neurosci 18:1250–1260.
- Mook-Jung I, Gordon H (1996): Acteylcholine receptor clustering associates with proteoglycan biosynthesis in C2 variant and heterokaryon muscle cells. J Neurobiol 31:210–218.
- Mook-Jung I, Gordon H (1995): Acetylcholine receptor clustering in C2 muscle cells requires chondroitin sulfate. J Neurobiol 28:482–492.
- Nitkin RM, Smith MA, Magill C, Fallon JR, Yao YM, Wallace BG, McMahan UJ (1987): Identification of agrin, a synaptic organizing protein from Torpedo electric organ. J Cell Biol 105:2471–2478.
- Noonan DM, Malamud DJ, Przybylski RJ (1986): Biosynthesis of heparan sulfate proteoglycans of developing chick breast muscle in vitro. Exp Cell Res 166:327–339.
- O’Toole JJ, Deyst KA, Bowe MA, Nastuk MA, McKechnie BA, Fallon JR (1996): Alternative splicing of agrin regulates its binding to heparin, α-dystroglycan, and the cell surface. Proc Natl Acad Sci USA 93:7369–7374.
- Pacifici M, Molinaro M (1980): Developmental changes in glycosaminoglycans during skeletal muscle cell differentiation in culture. Exp Cell Res 126:143–152.
- Peng HB (1986): Elimination of preexistent acetylcholine receptor clusters induced by the formation of new clusters in the absence of nerve. J Neurosci 6:581–589.
- Ravdin P, Axelrod D (1977): Fluorescent tetramethyl rhodamine derivatives of alpha-bungarotoxin: Preparation, separation, and characterization. Anal Biochem 80:585–592.
Roden L (1980): Structure and metabolism of connective tissue proteoglycans; in Lennars WJ (ed): The Biochemistry of Glycoproteins and Proteoglycans. New York, Plenum Press, pp 267–371.
- Sanes JR, Chiu AY (1983): The basal lamina of the neuromuscular junction. Cold Spring Harbor Symp Quant Biol 48:667–678.
- Sugiyama J, Bowen DC, Hall ZW (1994): Dystroglycan binds nerve and muscle agrin. Neuron 13:103–115.
- Sugiyama JE, Glass DJ, Yancopoulos GD, Hall ZW (1997): Laminin-induced acetylcholine receptor clustering: An alternative pathway. J Cell Biol 139:181–191.
- Tsen G, Halfter W, Kroger S, Cole GJ (1995): Agrin is a heparan sulfate proteoglycan. J Biol Chem 270:3392–3399.
- Valenzuela DM, Stitt TN, DeStefano PS, Rojas E, Mattsson K, Compton DL, Nunez L, Park JS, Stark JL, Gies DR, Thomas S, LeBeau MM, Fernald AA, Copeland NG, Jenkins NA, Burden SJ, Yancopolous GD (1995): Receptor tyrosine kinase specific for the skeletal muscle lineage: Expression in embryonic muscle, at the neuromuscular junction, and after injury. Neuron 15:573–584.
- Vogel Z, Christian CN, Vigny M, Bauer HC, Sonderegger P, Daniels MP (1983): Laminin induces acetylcholine receptor aggregation on cultured myotubes and enhances the receptor aggregation activity of a neuronal factor. J Neurosci 3:1058–1068.
- Wallace BG (1990): Inhibition of agrin-induced acetylcholine receptor aggregation by heparin, heparan sulfate, and other polyanions. J Neurosci 10:3576–3582.
- Wallace BG, Qu Z, Huganir RL (1991): Agrin induces phosphorylation of the nicotinic acetylcholine receptor. Neuron 6:869–78.
- Weston C, Gordon C, Teressa G, Hod E, Ren X-D, Prives J (2003): Cooperative regulation by Rac and Rho of agrin-induced acetylcholine receptor clustering in muscle cells. J Biol Chem 278:6450–6455.
- Willmann R, Fuhrer C (2002): Neuromuscular synaptogenesis: Clustering of acetylcholine receptors revisited. Cell Mol Life Sci 59:1296–1316.
- Yaffe D, Saxel O (1977): Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature 270:725–727.
- Yamaguchi Y (2002): Glycobiology of the synapse: The role of glycans in the formation, maturation, and modulation of synapses. Biochim Biophys Acta 1573:369–376.
- Yurchenco PD, Schittny JC (1990): Molecular architecture of basement membranes. FASEB J 4:1577–1590.
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