The acetylcholine receptor: Its molecular biology and biotechnological prospects

The structure and behaviour of the acetylcholine receptor (AChR) is described, and the evidence that it is an allosteric protein is discussed. The genes for the AChR subunits are subject to a complex set of spatio‐temporal transcriptional controls during development of the motor endplate, and these findings are reviewed here. Finally, the biotechnological prospects suggested by the new data are noted.

[1]  J P Changeux,et al.  Localization of nicotinic acetylcholine receptor alpha-subunit transcripts during myogenesis and motor endplate development in the chick , 1989, The Journal of cell biology.

[2]  J. Changeux,et al.  Interaction of nuclear factors with the upstream region of the alpha‐subunit gene of chicken muscle acetylcholine receptor: variations with muscle differentiation and denervation. , 1989, The EMBO journal.

[3]  H. Lester,et al.  Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor. , 1988, Science.

[4]  S. Oiki,et al.  M2 delta, a candidate for the structure lining the ionic channel of the nicotinic cholinergic receptor. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[5]  B. Sakmann,et al.  Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance , 1988, Nature.

[6]  N. Unwin,et al.  Arrangement of the acetylcholine receptor subunits in the resting and desensitized states, determined by cryoelectron microscopy of crystallized Torpedo postsynaptic membranes , 1988, The Journal of cell biology.

[7]  M. Ballivet,et al.  A cell type-specific enhancer drives expression of the chick muscle acetylcholine receptor α-subunit gene , 1988, Neuron.

[8]  J. Gershoni,et al.  Molecular decoys: ligand-binding recombinant proteins protect mice from curarimimetic neurotoxins. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Changeux,et al.  Amino acids of the Torpedo marmorata acetylcholine receptor alpha subunit labeled by a photoaffinity ligand for the acetylcholine binding site. , 1988, Biochemistry.

[10]  J. Changeux,et al.  Photoaffinity labeling of the acetylcholine binding sites on the nicotinic receptor by an aryldiazonium derivative. , 1988, Biochemistry.

[11]  J P Changeux,et al.  Detection of the nicotinic acetylcholine receptor alpha‐subunit mRNA by in situ hybridization at neuromuscular junctions of 15‐day‐old chick striated muscles. , 1988, The EMBO journal.

[12]  S. Heinemann,et al.  Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[13]  B. Sakmann,et al.  Differential regulation of muscle acetylcholine receptor γ‐and ϵ‐subunit mRNAs , 1987 .

[14]  J P Changeux,et al.  Calcitonin gene-related peptide and muscle activity regulate acetylcholine receptor alpha-subunit mRNA levels by distinct intracellular pathways , 1987, The Journal of cell biology.

[15]  P. Seeburg,et al.  Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family , 1987, Nature.

[16]  E. Gundelfinger,et al.  The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors , 1987, Nature.

[17]  J. Changeux,et al.  Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: [3H]chlorpromazine labels homologous residues in the beta and delta chains. , 1987, Biochemistry.

[18]  J. Schmidt,et al.  Quantitation of an alpha subunit splicing intermediate: evidence for transcriptional activation in the control of acetylcholine receptor expression in denervated chick skeletal muscle , 1987, The Journal of cell biology.

[19]  J. Changeux,et al.  Calcitonin gene‐related peptide elevates cyclic AMP levels in chick skeletal muscle: possible neurotrophic role for a coexisting neuronal messenger. , 1987, The EMBO journal.

[20]  J. Changeux,et al.  A 5'-flanking region of the chicken acetylcholine receptor alpha-subunit gene confers tissue specificity and developmental control of expression in transfected cells , 1987, Molecular and cellular biology.

[21]  B. Sakmann,et al.  Location of a δ-subunit region determining ion transport through the acetylcholine receptor channel , 1986, Nature.

[22]  T. Hökfelt,et al.  Calcitonin gene-related peptide, a peptide present in spinal cord motoneurons, increases the number of acetylcholine receptors in primary cultures of chick embryo myotubes , 1986, Neuroscience Letters.

[23]  J. Changeux,et al.  Characterization of the transient agonist-triggered state of the acetylcholine receptor rapidly labeled by the noncompetitive blocker [3H]chlorpromazine: additional evidence for the open channel conformation. , 1986, Biochemistry.

[24]  F. Lottspeich,et al.  The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices M II of the receptor subunits , 1986 .

[25]  J. Changeux,et al.  Effects of chlorpromazine and phencyclidine on mouse C2 acetylcholine receptor kinetics. , 1986, The Journal of physiology.

[26]  T. Usdin,et al.  Purification and characterization of a polypeptide from chick brain that promotes the accumulation of acetylcholine receptors in chick myotubes , 1986, The Journal of cell biology.

[27]  J. Changeux,et al.  Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: serine-262 of the delta subunit is labeled by [3H]chlorpromazine. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Miriam M. Salpeter,et al.  Nicotinic acetylcholine receptors in vertebrate muscle: Properties, distribution and neural control , 1985, Progress in Neurobiology.

[29]  J. Sanes,et al.  Concentration of acetylcholine receptor mRNA in synaptic regions of adult muscle fibres , 1985, Nature.

[30]  J. Changeux,et al.  Activity regulates the levels of acetylcholine receptor alpha-subunit mRNA in cultured chicken myotubes. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Dwork,et al.  Identification of the alpha subunit half-cystine specifically labeled by an affinity reagent for the acetylcholine receptor binding site. , 1984, The Journal of biological chemistry.

[32]  J. Changeux,et al.  Nicotinic receptor of acetylcholine: structure of an oligomeric integral membrane protein. , 1984, Physiological reviews.

[33]  J. Changeux,et al.  Time-resolved photolabeling by the noncompetitive blocker chlorpromazine of the acetylcholine receptor in its transiently open and closed ion channel conformations. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[34]  J. Changeux,et al.  Rapid kinetics of agonist binding and permeability response analyzed in parallel on acetylcholine receptor rich membranes from Torpedo marmorata. , 1983, Biochemistry.

[35]  J. Changeux,et al.  Multiple sites of action for noncompetitive blockers on acetylcholine receptor rich membrane fragments from torpedo marmorata. , 1983, Biochemistry.

[36]  J. Changeux,et al.  Complete mRNA coding sequence of the acetylcholine binding alpha-subunit of Torpedo marmorata acetylcholine receptor: a model for the transmembrane organization of the polypeptide chain. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Takashi Miyata,et al.  Structural homology of Torpedo californica acetylcholine receptor subunits , 1983, Nature.

[38]  S. Heinemann,et al.  Nucleotide and deduced amino acid sequences of Torpedo californica acetylcholine receptor gamma subunit. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[39]  J. Changeux,et al.  Functional Organization of the Acetylcholine Receptor: A Model of Ligand Gated Ion Channel , 1988 .

[40]  Menek Goldstein,et al.  Chapter 4 Coexistence of neuronal messengers — an overview , 1986 .

[41]  A. Mudge,et al.  Calcitonin gene-related peptide regulates muscle acetylcholine receptor synthesis , 1986, Nature.

[42]  P. Taylor,et al.  Topography of the Acetylcholine Receptor Revealed by Fluorescence Energy Transfer , 1986 .

[43]  R. Stroud,et al.  Acetylcholine receptor structure, function, and evolution. , 1985, Annual review of cell biology.