Abstract
The nicotinic acetylcholine receptor (AChR) is one of a family of ion channel receptors, which are gated directly by neurotransmitters. Other receptors of this type include the GABA and glycine receptors. An important characteristic of these receptors is that they are composed of multiple distinct subunits all of which have a similar transmembrane topology (for a review see Barnard et al., 1987). The AChR is an oligomeric glycoprotein consisting of five subunits (α2,β,γ, and δ) of four different types. Five subunits span the plasma membrane and are arranged in a rosette to form an ion channel. The binding of acetylcholine (ACh) to the a subunits causes the membrane channel to open (for reviews see Karlin, 1980; Conti-Tronconi & Raftery,1982; Barrantes,1983; Anholt et al.,1984, and Popot & Changeux,1984). Each of the four subunits is coded by separate mRNAs. Thus, the production of a complete functional AChR molecule involves complex processes including not only the synthesis of the individual subunits but also their assembly in a particular order, and their insertion into the plasma membrane with the correct orientation (for a review see Merlie & Smith, 1986).
This is a preview of subscription content, log in via an institution to check access.
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
Anderson, D. J. & Blobel, G. (1981) In vitro synthesis, glycosylation, and membrane insertion of the four subunit of Torpedo acetylcholine receptor. Proc. Natl. Acad. Sci. USA 78, 5598–5602.
Anholt, R., Lindstrom, J. & Montal. M. (1984) The molecular basis of neurotransmission: structure and function of the nicotinic acetylcholine receptor. In: The Enzymes of Biological Membranes, Ed. Martonosi, A. Vol. 3, pp 335–401, Plenum Press, New York.
Barnard, E.A., Miledi, R. & Sumikawa, K. (1982) Translation of exogenous messenger RNA coding for nicotinic acetylcholine receptors produces functional receptors in Xenopus oocytes. Proc. R. Soc. Lond. B215, 241–246.
Barnard, E.A., Darlison, M.G. & Seeburg, P. (1987) Molecular biology of the GABA receptor: the receptor/channel superfamily. Trends Neurosci. 10, 502–509.
Barrantes, F.J, (1983) Recent developments in the structure and function of acetylcholine receptor. Int. Rev. Neurobiol. 24, 259–341.
Blount, P. & Merlie, J. P. (1988) Native folding of an acetylcholine receptor a subunit expressed in the absence of other receptor subunits. J. Biol. Chem. 263, 1072–1080.
Carlin, B.E., Lawrence, J. C., Lindstrom, J. M. & Merlie, J. P. (1986) An acetylcholine receptor precursor a subunit that binds α-bungarotoxin but not d-tubocurarine. Proc. Natl. Acad. Sci. USA 83, 498–502.
Claudio, T., Ballivet, M., Patrick, J. & Heinemann, S. (1983) Nucleotide and deduced amino acid sequences of Torpedocalifornica acetylcholine receptor 7 subunit. Proc. Natl. Acad. Sci. USA 80, 1111–1115.
Claudio, T., Green, W. N., Hartman, D. S., Hayden, D., Paulson, H. L., Sigworth, F. J., Sine, S. M., & Swedlund, A. (1987) Genetic reconstitution of functional acetylcholine receptor channels in mouse fibroblasts. Science, 238, 1688–1694.
Conti-Tronconi, B.M. & Raftery, M.A. (1982) The nicotinic cholinergic receptor: correlation of molecular structure with functional properties. Ann. Rev. Biochem. 51, 491–530.
Dascal, N. (1987) The use of Xenopus oocytes for the study of ion channels. CRC Crit. Rev. Biochem. 22, 317–387.
Fujita, N., Nelson, N., Fox, T., Claudio, T., Lindstrom, J., Reizman, H. & Hess, G. (1986) Biosynthesis of the Torpedocalifornica receptor a subunit in yeast. Science, 231, 1284–1287.
Gershoni, J. M., Hawrot, E. & Lentz, T. L. (1983) Binding of a-bungarotoxin to isolated a subunit of the acetylcholine receptor of Torpedo californica: quantitative analysis with protein blots. Proc. Natl. Acad. Sci. USA 80, 4973–4977.
Green, P. J., Pines, 0. & Inouye, M. (1986) The role of antisense RNA in gene regulation. Annu. Rev. Biochem. 55, 569–597.
Haggerty, J. G. & Froehner, S. C. (1981) Restoration of 125I-α-bungarotoxin binding activity to the α-subunit of Torpedo acetylcholine receptor isolated by gel electrophoresis in sodium dodecyl sulfate. J. Biol. Chem. 256, 8294–8297.
Harland, R. & Weintraub, H. (1985) Translation of mRNA injected into Xenopus oocytes is specifically inhibited by antisense RNA. J. Cell. Biol. 101, 1094–1099.
Karlin, A. (1980) Molecular properties of nicotinic acetylcholine receptors. In: Cell Surface and Neuronal Function. Eds. Cotman, C.W., Poste, G. & Nicolson, G.L. Vol. 6, pp. 192–260, Elsevier Biomedical, Amsterdam, New York.
Kurosaki, T., Fukuda, K., Konno, T., Mori, Y., Tanaka, K., Mishina, M. & Numa, S. (1987) Functional properties of nicotinic acetylcholine receptor subunits expressed in various combinations. FEBS Letts. 214, 253–258.
Melton, D. (1985) Injected anti-sense RNAs specifically block messenger RNA translation in vivo. Proc. Natl. Acad. Sci. U.S.A. 82, 144–148.
Merlie, J.P., Sebbane, R., Tzartos, S. & Lindstrom, J. (1982) Inhibition of glycosylation with tunicamycin blocks assembly of newly synthesized acetylcholine receptor subunits in muscle cells. J. Biol. Chem. 257, 2694–2701.
Merlie, J.P. & Lindstrom, J. (1983) Assembly in vivo of mouse muscle acetylcholine receptor: identification of an a subunit species that may be an assembly intermediate. Cell, 34, 747–757.
Merlie, J. P. & Smith, M. M. (1986) Synthesis and assembly of acetylcholine receptor, a multisubunit membrane glycoprotein. J. Memb. Biol. 91, 1–10.
Miledi, R. & Sumikawa, K. (1982) Synthesis of cat muscle acetylcholine receptors by Xenopus oocytes. Biomed. Res. 3, 390–399.
Miledi, R., Parker, I. & Sumikawa, K. (1982) Properties of acetylcholine receptors translated by cat muscle mRNA in Xenopus oocytes. EMBO J. 1, 1307–1312.
Miledi, R., Parker, I. & Sumikawa, K (1988) Transplanting receptors from brains into oocytes. In: Fidia Award Lecture Series. Ed. Smith, J., Raven Press (in press).
Mishina, M., Tobimatsu, T., Imoto, K., Tanaka, K., Fujita, Y., Fukuda, K., Kurasaki, M., Takahashi, H., Morimoto, Y., Hirose, T., Inazama, S., Takahashi, T., Kuno, M. & Numa, S. (1985) Location of functional regions of acetylcholine receptor a-subunit by site-directed mutagenesis. Nature, 313, 364–369.
Oblas, B., Boyd, N. D. & Singer, R. H. (1983) Analysis of receptor-ligand interactions using nitrocellulose gel transfer: application to Torpedo acetylcholine receptor and alpha-bungarotoxin. Anal. Biochem. 130, 1–8.
Popot, J-L. & Changeux, J-P. (1984) Nicotinic receptor of acetylcholine: structure of an oligomeric integral membrane protein. Physiol. Rev. 64, 1162–1239.
Prives, J.M. & Olden, K. (1980) Carbohydrate requirement for expression and stability of acetylcholine receptor on the surface of embryonic muscle cells in culture. Proc. Natl. Acad. Sci. USA 77, 5263–5267.
Sadler, S.E. & Mailer, J.L. (1981) Identification of a steroid receptor on the surface of Xenopus oocytes by photoaffinity labeling. J. Biol. Chem. 256, 6368–6373.
Sumikawa, K., Houghton, M., Emtage, J.S., Richards, B.M. & Barnard, E.A. (1981) Active multi-subunit ACh receptor assembled by translation of heterologous mRNA in Xenopus oocytes. Nature, 292, 862–864.
Sumikawa, K., Parker, I. & Miledi, R. (1984) Separate fractions of mRNA from Torpedo electric organ induce chloride channels and acetylcholine receptors in Xenopus oocytes. EMBO J. 3, 2291–2294.
Sumikawa, K. & Miledi, R. (1988a) Repression of nicotinic acetylcholine receptor expression by antisense RNAs and an oligonucleotide. Proc. Natl. Acad. Sci. USA. 85, 1302–1306.
Sumikawa, K., & Miledi, R. (1988b) Assembly of all ACh receptor subunits is a prerequisite for their efficient insertion into plasma membranes, (submitted).
Sumikawa, K., & Miledi, R. (1988c) N-glycosylation of ACh receptor is required for insertion into plasma membranes, but not for subunit assembly, (submitted).
Tzartos, S. J., & Changeux, J.-P. (1983) High affinity binding of α-bungarotoxin to the purified a-subunit and to its 27,000-dalton proteolytic peptide from Torpedo marmorata. Requirement for sodium dodecyl sulfate. EMBO J. 2, 381–387.
White, M.M., Mayne, K.M., Lester, H.A. and Davidson, N. (1985) Mouse-Torpedo hybrid acetylcholine receptors: Functional homology does not equal sequence homology. Proc. Natl. Acad. Sci. USA, 82, 4852–4856.
Wilson, P. T., Lentz, T. L. & Hawrot, E. (1985) Determination of the primary amino acid sequence specifying the α bungarotoxin binding site on the α-subunit of the acetylcholine receptor from Torpedo californica. Proc. Natl. Acad. Sci. 82, 8790–8794.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Sumikawa, K., Miledi, R. (1989). Assembly and Insertion of a Multi-Subunit Nicotinic Acetylcholine Receptor into Plasma Membranes. In: Maelicke, A. (eds) Molecular Biology of Neuroreceptors and Ion Channels. NATO ASI Series, vol 32. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74155-5_38
Download citation
DOI: https://doi.org/10.1007/978-3-642-74155-5_38
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-74157-9
Online ISBN: 978-3-642-74155-5
eBook Packages: Springer Book Archive