Rapid upregulation of alpha7 nicotinic acetylcholine receptors by tyrosine dephosphorylation.
Alpha7 nicotinic acetylcholine receptors (nAChRs) modulate network activity in the CNS. Thus, functional regulation of alpha7 nAChRs could influence the flow of information through various brain nuclei. It is hypothesized here that these receptors are amenable to modulation by tyrosine phosphorylation. In both Xenopus oocytes and rat hippocampal interneurons, brief exposure to a broad-spectrum protein tyrosine kinase inhibitor, genistein, specifically and reversibly potentiated alpha7 nAChR-mediated responses, whereas a protein tyrosine phosphatase inhibitor, pervanadate, caused depression. Potentiation was associated with an increased expression of surface alpha7 subunits and was not accompanied by detectable changes in receptor open probability, implying that the increased function results from an increased number of alpha7 nAChRs. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated exocytosis was shown to be a plausible mechanism for the rapid delivery of additional alpha7 nAChRs to the plasma membrane. Direct phosphorylation/dephosphorylation of alpha7 subunits was unlikely because mutation of all three cytoplasmic tyrosine residues did not prevent the genistein-mediated facilitation. Overall, these data are consistent with the hypothesis that the number of functional cell surface alpha7 nAChRs is controlled indirectly via processes involving tyrosine phosphorylation.
Cho
Chang-Hoon
CH
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0021, USA.
Song
Weifeng
W
Leitzell
Katherine
K
Teo
Esther
E
Meleth
Annal D
AD
Quick
Michael W
MW
Lester
Robin A J
RA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D019921:Biotinylation / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002038:Bungarotoxins / Q000493:pharmacokinetics; D002794:Choline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D007328:Insulin / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008845:Microinjections / Q000379:methods; D016296:Mutagenesis / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D010744:Phosphoric Monoester Hydrolases / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050600:SNARE Proteins / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014638:Vanadates / Q000494:pharmacology; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007328:Insulin; D007456:Iodine Isotopes; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D050600:SNARE Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; D014638:Vanadates; D014443:Tyrosine; D016202:N-Methylaspartate; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010744:Phosphoric Monoester Hydrolases; D002794:Choline; D000109:Acetylcholine