Acetylcholine Receptor Related Genes Expressed in the Nervous System

Nef, Patrick; Oneyser, Carole; Barkas, T.; Ballivet, Marc

doi:10.1007/978-3-642-71649-2_31

Cited by 8 publications

(3 citation statements)

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“…Another clone, HYA23-1, was isolated from a cDNA library prepared from rat hypothalamus and represents a transcript of the alpha4 gene (2). In addition, a genomic clone containing an alpha2 gene has been isolated (9). These genes are expressed in the central nervous system, and we propose that the encoded proteins comprise the ligand-binding subunits of a family of neuronal acetylcholine receptors.…”

Section: Resultsmentioning

confidence: 99%

“…These bands may correspond to the proteins encoded by the clones we used in these expression studies. A chicken gene homologous to the rat alpha3 gene was isolated and sequenced by Ballivet and coworkers (9); in addition, they found clones encoding a protein that appears to be the product of an alpha2 gene (9), which they propose will contribute to the formation of yet another neuronal nicotinic receptor subtype.…”

Section: Discussionmentioning

confidence: 99%

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Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family.

Boulter

Connolly

Deneris

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

348

192

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A family of genes coding for proteins homologous to the a subunit of the muscle nicotinic acetylcholine receptor has been identified in the rat genome. These genes are transcribed in the central and peripheral nervous systems in areas known to contain functional nicotinic receptors. In this paper, we demonstrate that three of these genes, which we call alpha3, alpha4, and beta2, encode proteins that form functional nicotinic acetylcholine receptors when expressed in Xenopus oocytes. Oocytes expressing either alpha3 or alpha4 protein in combination with the beta2 protein produced a strong response to acetylcholine. Oocytes expressing only the alpha4 protein gave a weak response to acetylcholine. These receptors are activated by acetylcholine and nicotine and are blocked by Bungarus toxin 3.1. They are not blocked by a-bungarotoxin, which blocks the muscle nicotinic acetylcholine receptor. Thus, the receptors formed by the alpha3, alpha4, and beta2 subunits are pharmacologically similar to the ganglionic-type neuronal nicotinic acetylcholine receptor. These results indicate that the alpha3, alpha4, and beta2 genes encode functional nicotinic acetylcholine receptor subunits that are expressed in the brain and peripheral nervous system. It seems likely that complex brain functions, such as learning and memory, involve changes in the efficiency of synaptic transmission. One way in which synaptic efficiency might be modified is through a change in the availability or properties of neurotransmitter receptors in the postsynaptic membrane. Testing this idea, and understanding mechanisms that might accomplish such a modification, requires means of detecting and quantifying receptors at synapses in the central nervous system. However, the low abundance and great diversity of neurotransmitter receptors in the central nervous system have made their analysis difficult.We therefore chose first to study neurotransmitter receptors at the more accessible neuromuscular junction and were able to obtain and express cDNA clones encoding the subunits of the muscle-type nicotinic acetylcholine receptor of the rat. We subsequently used these cDNA clones to identify homologous genes that code for acetylcholine receptor a subunits found in the central nervous system. This approach led to the isolation of two new cDNA clones (1, 2) that represent gene transcripts found in different regions of the brain and that encode proteins with the general structural features of muscle nicotinic acetylcholine receptor a subunits. We proposed that these genes, called alpha3 and alpha4, code for the a subunits of functional nicotinic acetylcholine receptors expressed in the central and peripheral nervous systems. We have tested this hypothesis and in this paper report that RNA transcribed from either the clone derived from the alpha3 gene or the clone derived from the alpha4 gene, in concert with RNA transcribed from a new clone, PCX49, will direct the synthesis offunctional neuronal nicotinic acetylcholine receptors in Xenopus oocytes.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family.

Boulter

Connolly

Deneris

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

348

192

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“…Η διαλεύκανση της πρωτοταγούς δομής των τεσσάρων υπομονάδων του υποδοχέα απο το Torpedo californica (α, β, γ και δ) και η σύγκριση μεταξύ τους στο επίπεδο των 56 αμινο-τελικών αμινοξέων, κατέδειξε ένα σημαντικό ποσοστό ομολογίας της τάξεως του 35-50%, που μαρτυρά πως πρόκειται για εξελικτικά συγγενείς πρωτεΐνες (Raftery et al, 1980;Noda et al, 1983β). Παρόμοια ποσοστά ομολογίας αμινοξικών καταλοίπων μεταξύ των διαφορετικών υπομονάδων καταγράφηκαν και σε άλλα είδη όπως και στον άνθρωπο (Nef et al, 1986). Η σύγκριση αμινοξικών αλληλουχιών της ίδιας υπομονάδας μεταξύ διαφορετικών ειδών κατέδειξε ακόμα υψηλότερα ποσοστά ομολογίας.…”

Section: η δομή του υποδοχέα της ακετυλοχολίνηςunclassified

Ανασυνδυασμένα Τμήματα Του Ανθρώπινου Νικοτινικού Υποδοχέα Για Την Κατανόηση Των Παθογενετικών Μηχανισμών Της Βαριάς Μυασθένειας

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