title: Ly6h regulates trafficking of alpha7 nicotinic acetylcholine receptors and nicotine-induced potentiation of glutamatergic signaling.
abstract: α7 nAChRs are expressed widely throughout the brain, where they are important for synaptic signaling, gene transcription, and plastic changes that regulate sensory processing, cognition, and neural responses to chronic nicotine exposure. However, the mechanisms by which α7 nAChRs are regulated are poorly understood. Here we show that trafficking of α7-subunits is controlled by endogenous membrane-associated prototoxins in the Ly6 family. In particular, we find that Ly6h reduces cell-surface expression and calcium signaling by α7 nAChRs. We detect Ly6h in several rat brain regions, including the hippocampus, where we find it is both necessary and sufficient to limit the magnitude of α7-mediated currents. Consistent with such a regulatory function, knockdown of Ly6h in rat hippocampal pyramidal neurons enhances nicotine-induced potentiation of glutamatergic mEPSC amplitude, which is known to be mediated by α7 signaling. Collectively our data suggest a novel cellular role for Ly6 proteins in regulating nAChRs, which may be relevant to plastic changes in the nervous system including rewiring of glutamatergic circuitry during nicotine addiction.
authors.affiliation: Department of Pharmacology.
authors.forename: Clare A
authors.initials: CA
authors.lastname: Puddifoot
authors.affiliation: Department of Pharmacology.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Pharmacology.
authors.forename: Rou-Jia
authors.initials: RJ
authors.lastname: Sung
authors.affiliation: Department of Pharmacology, Biomedical Sciences Graduate Program, Neurosciences Graduate Program, and Center for Circadian Biology, University of California San Diego, La Jolla, California 92093-0636 wjoiner@ucsd.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Joiner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000494:pharmacology; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D017774:Long-Term Potentiation; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D055369:Miniature Postsynaptic Potentials; D008969:Molecular Sequence Data; D018722:Nicotinic Agonists / Q000494:pharmacology; D021381:Protein Transport; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: C121774:Ly6H protein, mouse; D008562:Membrane Glycoproteins; D018722:Nicotinic Agonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; D018698:Glutamic Acid
keywords: Ly6; acetylcholine receptor; modulation; nicotine; plasticity; trafficking