Acetylcholine Receptor-Expressing Fibroblasts

  • Toni Claudio
Conference paper
Part of the NATO ASI Series book series (volume 38)


Two key and as yet unresolved questions concerning the autoimmune disease myasthenia gravis (MG) are: 1) what initiates the autoimmune response, and 2) what sustains it. It is known that autoantibodies to the acetylcholine receptor (AChR) can be detected in MG patient sera, that the disease symptoms can be passively transferred from humans to mice with the IgG fraction from MG patient sera (Drachman et al. 1976), that the AChR can induce experimental autoimmune myasthenia gravis (EAMG) in test animals (reviewed in Lindstrom 1985; Newsom-Davis 1986; Engel 1987), and that the AChR is the only protein at endplates which is capable of inducing EAMG (Claudio & Raftery 1980). The importance of the AChR in this disease cannot be disputed, but what role does it play in the initiation and/or maintenance of the disease. Are there specific epitopes on the AChR that are required for induction? It has been suggested that alterations of AChRs on myoid cells in the thymus might serve to break tolerance and initiate the autoimmune response directed against AChRs. Penicillamine has been shown to react with AChRs and to enhance EAMG (Bever et al. 1984). If alterations in the AChR can cause MG, do they occur by an exogenous or an endogenous mechanism? An endogenous mechanism acting directly on AChRs could have several sites of action. Various posttranslational modifications of the AChR are known to occur naturally, including disulfide-bond formation, glycosylation, phosphorylation, and fatty acylation.


Selectable Marker Gene Single Channel Recording AChR Cluster Subunit cDNAs AChR Subunit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bever CT, Dretchen KL, Blake GJ, Chang HW, Asofsky R (1984) Augmented anti-acetylcholine receptor response following long-term penicillamine admisistration. Ann Neurol 16: 9–13PubMedCrossRefGoogle Scholar
  2. Blau HM, Chiu C-P, Webster C (1983) Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell 32: 1171–1180PubMedCrossRefGoogle Scholar
  3. Claudio T (1987) Stable expression of transfected Torpedo acetylcholine receptor a-subunits in mouse fibroblast L cells. Proc Natl Acad Sci USA 84: 5967–5971PubMedCrossRefGoogle Scholar
  4. Claudio T (1989) Molecular genetics of acetylcholine receptor-channels. In: Glover DM, Hames D (eds) Frontiers in Molecular Biology. IRL Press, London (in press)Google Scholar
  5. Claudio T, Raftery MA (1980) Is experimental autoimmune myasthenia gravis induced only by acetylcoline receptors? J Immunol 124: 1130–1140PubMedGoogle Scholar
  6. Claudio T, Green WN, Hartman D, Hayden D, Paulson HL, Sigworth FJ, Sine SM, Swedlund A (1987) Genetic reconstitution of functional acetylcholine receptor-channels in mouse fibroblasts. Science 238: 1688–1694PubMedCrossRefGoogle Scholar
  7. Claudio T, Paulson HL, Hartman D, Sine S, and Sigworth FJ (1989a) Establishing a stable expression system for studies of acetylcholine receptors. In: Hoffman JF, Giebisch G (eds) Current Topics in Membranes and Transport, Molecular Biology of Ion Channels, vol 33. Academic Press, New York, p 219–247CrossRefGoogle Scholar
  8. Claudio T, Hartman DS, Green WN, Ross AF, Paulson HL, Hayden D (1989b) Stable expression of multisubunit protein complexes in mammalian cells. In: Maelicke A (ed) NATO ASI Series H, Cell Biology, Molecular Biology of Neuroreceptors and Ion Channels, vol 32. Springer-Verlag, Berlin, p 469–480Google Scholar
  9. Claudio T, Paulson HL, Green WN, Ross AF, Hartman DS, Hayden D (1989c) Fibroblasts transfected with Torpedo acetylcholine receptor β, γ, and s subunit cDNAs express functional AChRs when infected with a retroviral α-recombinant. J Cell Biol 108 (in press)Google Scholar
  10. Conti-Tronconi, BM, Raftery MA (1982) The nicotinic cholinergic receptor: correlation of molecular structure with functional properties. Ann Rev Biochem 51: 491–530PubMedCrossRefGoogle Scholar
  11. Davies J, Jimenez A (1980) A new selective agent for eukaryotic cloning vectors. Am J Trop Med Hyg (Suppl) 29: 1089–1092Google Scholar
  12. Drachman D, Kao J, Pestronk A,Toyka K (1976) Myasthenia gravis as a receptor disorder. Ann NY Acad Sci 274: 226–234PubMedCrossRefGoogle Scholar
  13. Engel, AG (1987) Molecular biology of endplate diseases. In: Salpetyer, MM (ed) The Vertebrate Neuromuscular Junction. Alan R Liss, Inc., New York, p 361–424Google Scholar
  14. Graham R, van der Eb A (1973) A new technique for the assay of infectivity of human adenovirus 5 virus. Virol 52: 456–467CrossRefGoogle Scholar
  15. Green WN, Claudio T (1988) Differences in the phosphorylation of unassembled, assembled but cytoplasmic, and surface acetylcholine receptors. Soc Neurosci Abstr 14:1045 (419.3)Google Scholar
  16. Hartman DS, Poo M-m, Green WN, Ross AF, Claudio T (1989) Synaptic contact between embryonic neurons and acetylcholine receptor-fibroblasts J Physiol Paris (in press)Google Scholar
  17. Huganir RL, Greengard P (1987) Regulation of receptor function by protein phosphorylation. Trends in Pharm Sci 8: 472–477CrossRefGoogle Scholar
  18. Karlin A (1980) Molecular properties of nicotinic acetylcholine receptors. In: Cotman CW, Poste G, Nicolson GL (eds) The Cell Surface and Neuronal Function, vol 6. Elsevier/North-Holland Biomedical Press, Amsterdam, p 191–260Google Scholar
  19. Lindstrom J (1985) Immunobiology of myasthenia gravis, experimental autoimmune myasthenia gravis, and lambert-eaton syndrome. Ann Rev Immunol 3: 109–131CrossRefGoogle Scholar
  20. Mann R, Mulligan RC, Baltimore D (1983) Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 33: 153–159PubMedCrossRefGoogle Scholar
  21. Newsom-Davis, J (1986) Diseases of the neuromuscular junction. In: Asbury RK, Guy M, McKhann W, McDonald I (eds) Diseases of the Nervous System, Clinical Neurobiology, vol I. Ardmore Medical Books, Philadelphia, p 269–282Google Scholar
  22. Paulson HL, Claudio T (1988) Temperature-sensitive expression of all-Torpedo and Torpedo-rat hybrid AChRs in mammalian cells. Soc Neurosci Abstr 14:1045 (419.4)Google Scholar
  23. Popot J-L, Changeux P-J (1984) Nicotinic receptor of acetylcholine: structure of an oligomeric integral membrane protein. Physiol Rev 64: 1162–1239PubMedGoogle Scholar
  24. Ross AF, Rapuano M, Prives JM (1988) Induction of phosphorylation and cell surface redistribution of acetylcholine receptors by phorbol ester and carbamylcholine in cultured chick myotubes J Cell Biol 107: 1139–1145PubMedCrossRefGoogle Scholar
  25. Rubin LL, Barald KF (1983) Neuromuscular development in tissue culture. In: Burnstock G, Vrbova G, O’Brien R (eds) Somatic and Autonomic Nerve-Muscle Interactions. Elsevier Science Publisher, BV, Amsterdam, New York, p 109–151Google Scholar
  26. Rubin LL, McMahan UJ (1982) Regeneration of the neuromuscular junction: steps toward defining the molecular basis of the interaction between nerve and muscle. In: Schotland DL (ed) Disorders of the Motor Unit. John Wiley & Sons, p 187–196Google Scholar
  27. Schubert D, Harris AJ, Devine CE, Heinemann S (1974) Characterization of a unique muscle cell line. J Cell Biol 61: 398–413PubMedCrossRefGoogle Scholar
  28. Schuetze SM, Role L (1987) Developmental regulation of nicotinic acetylcholine receptors. Ann Rev Neurosci 10: 403–457PubMedCrossRefGoogle Scholar
  29. Subramani S, Mulligan RC, Berg P (1981) Expression of the mouse dihydrofolate reductase cDNA in simian virus 40 vectors. Mol Cell Biol 1: 854–864PubMedGoogle Scholar
  30. Wigler M, Silverstein S, Lee L-S, Pellicer A, Cheng Y-c, Axel R (1977) Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells. Cell 11: 223–232PubMedCrossRefGoogle Scholar
  31. Yaffe D (1968) Retention of differentiation potentialities during prolonged cultivation of myogenic cells. Proc Natl Acad Sci USA 61: 477–483PubMedCrossRefGoogle Scholar
  32. Yaffe D, Saxel O (1977) Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature 270: 725–727PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • Toni Claudio
    • 1
  1. 1.Department of Cellular & Molecular PhysiologyYale University School of MedicineNew HavenUSA

Personalised recommendations