Brain α-bungarotoxin binding protein cDNAs and MAbs reveal subtypes of this branch of the ligand-gated ion channel gene superfamily

Schoepfer, Ralf; Conroy, William G.; Whiting, Paul J.; Gore, Martin; Lindstrom, Jon

doi:10.1016/0896-6273(90)90031-a

Cited by 450 publications

(344 citation statements)

References 66 publications

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“…The precise spatial relationship between the key residues contributing to the receptor binding site [21,22] may vary among receptor subtypes and hence could influence the affinity of binding of MLA. Sequence analysis of the two (Ybungarotoxin binding proteins recently cloned from chick brain [7] shows them to have lower homology with other avian nicotinic receptor subunits (less than 50% in every case [7]) than there is between neuronal and muscle nicotinic receptor subunits. That is to say, within the same species the enigmatic brain abungarotoxin binding protein is less similar to the muscle nicotinic receptor, which also binds a-bungarotoxin (see Fig.…”

Section: Resultsmentioning

confidence: 97%

“…In view of the current uncertainty about the physiological status of ['251]cu-bungarotoxin binding sites in the mammalian CNS (see [6,7]), a pharmacological probe showing selectivity for this site would be very useful. Although the rw-bungarotoxin binding component in vertebrate brain shows homology with nAChR at the protein [S] and gene [7] level, there is little direct evidence that this protein has any role in synaptic transmission in the brain, despite its clear nicotinic pharmacology in binding experiments. Exceptions include the chick optic tectum [S] and cerebellar interneurones [9], where ~-bungarotoxin has been shown to antagonize nicotinic responses.…”

Section: Introductionmentioning

confidence: 99%

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Methyllycaconitine: a selective probe for neuronal α‐bungarotoxin binding sites

et al. 1990

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The ability of methylly~conitine (MLA) to inhibit the binding of ezsI~-bungarotoxin to rat brain membranes, frog and human muscle extracts and the human muscle cell line TE671 has been measured. MLA showed a markedly higher affinity for the rat brain site (Ki 1.4 x IO* M) than for the muscle receptors (4 1O-s-1O-6 M). Structure modelling techniques were used to fit the structure of MLA to a nicotinic pharmacophore model. MLA is the first low molecular weight ligand to be shown to discriminate between muscle nicotinic receptors and their a-bungarotoxinbinding counterpart in the brain, and as such may be a useful structural probe for pursuing the structural and functional properties of the neuronal protein.Methylly~~onitine; Nicotinic receptor; Brain a-bungarotoxin binding site; Nicotinic pharmacoph&z

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Methyllycaconitine: a selective probe for neuronal α‐bungarotoxin binding sites

et al. 1990

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“…A different possibility for the lack of rapid desensitization is that presynaptic ␣7-nAChRs may differ in composition from the homomeric ␣7-nAChR described previously (Couturier et al, 1990;Schoepfer et al, 1990;Chen and Patrick, 1997;Drisdel and Green, 2000). Heteromeric receptors containing the ␣7 and ␤2 gene products can be produced by heterologous coexpression, and the receptors have diminished rates of desensitization (Khiroug et al, 2002).…”

Section: Synaptic Options On Neurons Presynaptic Sitesmentioning

confidence: 97%

“…This regulation is made possible by the fact that all vertebrate nAChRs, including both muscle and neuronal receptors, are cation-selective ligand-gated ion channels with significant relative permeabilities to calcium. The most extreme appears to be that of nicotinic receptors containing the ␣7 gene product (Couturier et al, 1990;Schoepfer et al, 1990); they equal or exceed NMDA receptors in relative calcium permeability (Bertrand et al, 1993;Seguela et al, 1993). Such receptors (␣7-nAChRs) are one of the two most abundant nicotinic receptor subtypes expressed in brain (Sargent, 1993;Gotti et al, 1994;Lindstrom, 1996;Role and Berg, 1996;Conroy and Berg, 1998), and in contrast to NMDA receptors, they do not require the postsynaptic membrane to be depolarized before promoting calcium influx.…”

Section: Introductionmentioning

confidence: 99%

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

2002

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Nicotinic receptors are cation-ion selective ligand-gated ion channels that are expressed throughout the nervous system. Most have significant calcium permeabilities, enabling them to regulate calcium-dependent events. One of the most abundant is a species composed of the ␣7 gene product and having a relative calcium permeability equivalent to that of NMDA receptors. The ␣7-containing receptors can be found presynaptically where they modulate transmitter release, and postsynaptically where they generate excitatory responses. They can also be found in perisynaptic locations where they modulate other inputs to the neuron and can activate a variety of downstream signaling pathways. The effects the receptors produce depend critically on the sites at which they are clustered. Instructive preparations for examining ␣7-containing receptors are the rat hippocampus, where they are thought to play a modulatory role, and the chick ciliary ganglion, where they participate in throughput transmission as well as regulatory signaling. Relatively high levels of ␣7-containing receptors are found in the two preparations, and the receptors display a variety of synaptic options and functions in the two cases. Progress is starting to be made in understanding the mechanisms responsible for localizing the receptors at specific sites and in identifying components tethered in the vicinity of the receptors that may facilitate signal transduction and downstream signaling.

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“…of even only one (ay subunit) (Schoepfer et al 1990;Couturier et al 1990 a) in Xenopus oocytes suffices to yield a functional receptor which also desensitizes but may display an ionic selectivity (high permeability to Ca 2+ ) distinct from that of the muscle receptor Vernino et al 1992). On the basis of the primary amino acid sequence data of the purified subunits (Devillers-Thiery et al 1979;Raftery et al 1980), the cDNA and genes coding for the several subunits of electric organ and skeletal muscle receptor were cloned and sequenced (Noda et al 1982(Noda et al , 1983Claudio et al 1983;Devillers-Thiery et al 1983, Numa, 1989.…”

Section: The N I C O T I N I C Receptor Sitesmentioning

confidence: 99%

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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Brain α-bungarotoxin binding protein cDNAs and MAbs reveal subtypes of this branch of the ligand-gated ion channel gene superfamily

Cited by 450 publications

References 66 publications

Methyllycaconitine: a selective probe for neuronal α‐bungarotoxin binding sites

Methyllycaconitine: a selective probe for neuronal α‐bungarotoxin binding sites

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

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

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