Identification of calcium binding sites that regulate potentiation of a neuronal nicotinic acetylcholine receptor
| Autor: | Jean-Luc Galzi, Jean-Pierre Changeux, D. Bertrand, P.J. Corringer, S. Bertrand |
|---|---|
| Přispěvatelé: | Neurobiologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre médical universitaire de Genève (CMU), Récepteurs et Cognition (RC), Collège de France (CdF (institution))-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France (CdF (institution))-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 1996 |
| Předmět: |
cooperativity
[SDV]Life Sciences [q-bio] Xenopus MESH: Neurons neuronal nicotinic receptor Cooperativity MESH: Amino Acid Sequence Receptors Nicotinic 0302 clinical medicine MESH: Animals MESH: Xenopus Receptor ionic currents chemistry.chemical_classification Neurons 0303 health sciences Molecular Structure General Neuroscience MESH: Chickens Amino acid Nicotinic acetylcholine receptor MESH: Mutagenesis Site-Directed Biochemistry MESH: Calcium MESH: Receptors Nicotinic [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Female Research Article Agonist MESH: Mutation medicine.drug_class Recombinant Fusion Proteins MESH: Molecular Structure chemistry.chemical_element Biology Calcium In Vitro Techniques General Biochemistry Genetics and Molecular Biology MESH: Oocytes 03 medical and health sciences agonist affinity MESH: Terbium Consensus Sequence medicine MESH: Recombinant Fusion Proteins Animals calcium binding site MESH: Consensus Sequence Amino Acid Sequence Binding site Terbium Molecular Biology 5-HT receptor 030304 developmental biology MESH: In Vitro Techniques Binding Sites General Immunology and Microbiology chemistry MESH: Binding Sites Mutation Biophysics Mutagenesis Site-Directed Oocytes MESH: Female Chickens 030217 neurology & neurosurgery |
| Zdroj: | EMBO Journal EMBO Journal, EMBO Press, 1996, 15 (21), pp.5824-32 EMBO Journal, 1996, 15 (21), pp.5824-32 |
| ISSN: | 0261-4189 1460-2075 |
| Popis: | International audience; The divalent cation calcium potentiates the physiological response of neuronal nicotinic receptors to agonists by enhancing ionic current amplitudes, apparent agonist affinity and cooperativity. Here we show that mutations in several consensus Ca2+ binding sequences from the N-terminal domain of the neuronal alpha 7 nicotinic acetylcholine receptor alter Ca2+ potentiation of the alpha 7-V201-5HT3 chimera. Mutations E18Q or E44Q abolish calcium-enhanced agonist affinity but preserve the calcium increase of plateau current amplitudes and cooperativity. On the other hand, mutations of amino acids belonging to the 12 amino acid canonical domain (alpha 7 161-172) alter all features of potentiation by enhancing (D163, S169), reducing (E161, S165, Y167) or abolishing (E172) calcium effects on ionic current amplitudes and agonist affinity. Introduction of the alpha 7 161-172 domain in the calcium insensitive 5-hydroxytryptamine (5HT3) serotoninergic receptor results in a receptor activated by 5HT and potentiated by calcium. In vitro terbium fluorescence studies with an alpha 7 160-174 peptide further show that mutation E172Q also alters in vitro calcium binding. Data are consistent with the occurrence of distinct categories of regulatory calcium binding sites, among which the highly conserved (alpha 7 161-172) domain may simultaneously contribute to calcium and agonist binding. Images |
| Databáze: | OpenAIRE |
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