title: A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit.
abstract: We present herein the cloning of the human nicotinic acetylcholine receptor alpha9-ortholog and the identification of a new alpha-like subunit (alpha10) that shares 58% identity with alpha9. Whereas alpha10 fails to produce functional receptors alone, it promoted robust acetylcholine-evoked currents when coinjected with alpha9. The presence of alpha10 modifies the physiological and pharmacological properties of the alpha9 receptor indicating that the two subunits coassemble in a single functional receptor. Fusing the N-terminal domain of alpha9 with the rest of the alpha10-cDNA yielded a functional alpha9:alpha10-chimera that displays the acetylcholine binding properties of alpha9 and ionic pore characteristics of alpha10-containing receptors. In addition, alpha9- and alpha10-subunit mRNAs show limited similar tissue distribution patterns and are expressed in cochlea, pituitary gland, and keratinocytes. These data suggest that, in vivo, alpha9-containing receptors coassemble with alpha10-subunit.
authors.affiliation: Sanofi-Synthélabo, Department of Molecular and Functional Genomics, Rueil-Malmaison, France. frederic.sgard@sanofi-synthelabo.com
authors.forename: Frédéric
authors.initials: F
authors.lastname: Sgard
authors.forename: Eric
authors.initials: E
authors.lastname: Charpantier
authors.forename: Sonia
authors.initials: S
authors.lastname: Bertrand
authors.forename: Nancy
authors.initials: N
authors.lastname: Walker
authors.forename: Daniel
authors.initials: D
authors.lastname: Caput
authors.forename: David
authors.initials: D
authors.lastname: Graham
authors.forename: Daniel
authors.initials: D
authors.lastname: Bertrand
authors.forename: François
authors.initials: F
authors.lastname: Besnard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010802:Phylogeny; D021122:Protein Subunits; D011978:Receptors, Nicotinic / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D021122:Protein Subunits; D011978:Receptors, Nicotinic; C443079:nAChR alpha9