Mapping the Main Immunogenic Region and Toxin-Binding Site of the Nicotinic Acetylcholine Receptor

Barkas, T.; Mauron, Alex; Roth, Beat; Alliod, Christine; Tzartos, S.J.; Ballivet, Marc

doi:10.1126/science.2432658

Cited by 160 publications

(84 citation statements)

References 27 publications

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“…Torpedo AChR a-subunit cDNA clones have been expressed in fragments in bacteria [36,37], as full-length clones in yeast [38] and cell lines [39,40]. The proteins in bacteria have been used to map the aBgt-binding site [36,37] and epitopes recognized by T cells in experimental autoimmune MG (EAMG) and MG (Melmes, A. et al, personal communication).…”

Section: Discussionmentioning

confidence: 99%

The human medulloblastoma cell line TE671 expresses a muscle‐like acetylcholine receptor Cloning of the α‐subunit cDNA

1988

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Nicotinic acetylcboline receptors (AChRs) from muscle bind a-bungarotoxin (aBgt) and are composed of four kinds of subunits, whereas AChRs from mammalian brains do not bind aBgt and are composed of two kinds of subunits. aBgt-binding proteins whose function is unknown are also found in brain. All these proteins belong to the same gene family. The human medulloblastoma cell line TE671 expresses a functional AChR which binds aBgt. Surprisingly, the AChR of this neuron-derived cell line has electrophysiological, immunological and biochemical properties different from neuronal AChRs and very similar to muscle AChRs. The TE671 AChR binds crBgt, but is different from aBgt-binding proteins in brain. Here we show that TE671 expresses the a-subunit mRNA coding for the muscle AChR, thereby proving that TE671 expresses a muscle-type AChR that is not expressed in adult brain. The isolated cDNA clones should prove useful for expression of large amounts of human muscle-type AChR a-subunit protein for studies of the autoimmune response to muscle AChRs in human myasthenia gravis.

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Section: Discussionmentioning

confidence: 99%

The human medulloblastoma cell line TE671 expresses a muscle‐like acetylcholine receptor Cloning of the α‐subunit cDNA

1988

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“…This labelling, however, occurs exclusively on the reduced receptor since in the native receptor, Cysi92 and 193 are linked by a disulphide bridge (Kao & Karlin, 1986;Mosckovitz & Gershoni, 1988). Subsequent studies, based on the binding of snake a-toxins to a-subunit fragments, to synthetic peptides (Wilson et al, 1985;Radding et al, 1988;MulacJericevic & Atassi, 1986;Ralston et al 1987), deletion mutants (Barkas et al 1987), or a-subunit fragments expressed in Escherichia coli transformants (Gershoni, 1987), as site-directed mutagenesis experiments , confirmed that the region containing contributes to the interaction of cholinergic ligands and snake a-toxins with the a-subunit.…”

Section: Identification Of Amino Acids Composing the Binding Areas Fomentioning

confidence: 92%

The functional architecture of the acetylcholine nicotinic receptor explored by affinity labelling and site-directed mutagenesis

Changeux

Galzi

Devillers‐Thiéry

et al. 1992

Quart. Rev. Biophys.

180

100

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The scientific community will remember Peter Läuger as an exceptional man combining a generous personality and a sharp and skilful mind. He was able to attract by his views the interest of a large spectrum of biologists concerned by the mechanism of ion translocation through membranes. Yet, he was not a man with a single technique or theory. Using an authentically multidisciplinary approach, his ambition was to ‘understand transmembrane transport at the microscopic level, to capture its dynamics in the course of defined physiological processes’ (1987). According to him, ‘new concepts in the molecular physics of proteins’ had to be imagined, and ‘the traditional static picture of proteins has been replaced by the notions that proteins represent dynamic structures, subjected to conformational fluctuations covering a very wide time-range’ (1987).

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“…Bacteria have also been used to express recombinant nAChR subunits, despite bacterial cells lacking the machinery for appropriate post-translational processing. Indeed, specific binding of nicotinic radioligands such as [ 125 I]-α-bungarotoxin has been reported with bacterial-expressed subunit proteins [55,73,74]. Yeast cells have also been used as an expression system for nAChRs and have been shown to produce subunit proteins with molecular weights similar to those of native nAChRs, suggesting that nAChR subunits expressed in yeast undergo glycosylation and signal-sequence cleavage [75][76][77].…”

Section: Expression Of Recombinant Nachrs In Vitro and In Bacteria Anmentioning

confidence: 99%

A review of experimental techniques used for the heterologous expression of nicotinic acetylcholine receptors

Millar

2009

Biochemical Pharmacology

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Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop family of neurotransmitter-gated ion channels, a family that also includes receptors for γ-aminobutyric acid, glycine and 5-hydroxytryptamine. In humans, nAChRs have been implicated in several neurological and psychiatric disorders and are major targets for pharmaceutical drug discovery. In addition, nAChRs are important targets for neuroactive pesticides in insects and in other invertebrates. Historically, nAChRs have been one of the most intensively studied families of neurotransmitter receptors. They were the first neurotransmitter receptors to be biochemically purified and the first to be characterized by molecular cloning and heterologous expression. Although much has been learnt from studies of native nAChRs, the expression of recombinant nAChRs has provided dramatic advances in the characterization of these important receptors. This review will provide a brief history of the characterization of nAChRs by heterologous expression. It will focus, in particular, upon studies of recombinant nAChRs, work that has been conducted by many hundreds of scientists during a period of almost 30 years since the molecular cloning of nAChR subunits in the early 1980's.

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Mapping the Main Immunogenic Region and Toxin-Binding Site of the Nicotinic Acetylcholine Receptor

Cited by 160 publications

References 27 publications

The human medulloblastoma cell line TE671 expresses a muscle‐like acetylcholine receptor Cloning of the α‐subunit cDNA

The human medulloblastoma cell line TE671 expresses a muscle‐like acetylcholine receptor Cloning of the α‐subunit cDNA

The functional architecture of the acetylcholine nicotinic receptor explored by affinity labelling and site-directed mutagenesis

A review of experimental techniques used for the heterologous expression of nicotinic acetylcholine receptors

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