title: Regulation of AMPA receptor trafficking by O-glycosylation.
abstract: The present study investigated the role of O-linked beta-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) in AMPA receptor trafficking. Alloxan, an inhibitor of O-GlcNAc transferase, potentiated responses of AMPA receptors composed of the GluR1 subunit expressed in Xenopus oocytes. No potentiating effect of alloxan was obtained with mutant GluR1 (S831A) receptor lacking CaMKII phosphorylation site. Alloxan facilitated basal synaptic transmission to approximately 120% of basal levels and enhanced Schaffer collateral-CA1 long-term potentiation (LTP) in rat hippocampal slices, especially in the late phase of the LTP. Alloxan stimulated translocation of the GluR1 and GluR2 subunit from the cytosol towards the plasma membrane in rat hippocampal slices with the LTP, although it had no effect on subcellular distribution of the NR1 subunit. Taken together, the results of the present study show that alloxan regulates AMPA receptor trafficking by inhibiting O-GlcNAcylation, to modulate hippocampal synaptic transmission and synaptic plasticity.
authors.affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Tetsu
authors.initials: T
authors.lastname: Nagata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mukasa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D006031:Glycosylation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009865:Oocytes; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*; D014981:Xenopus
chemical_list: D000496:Alloxan; D017351:N-Acetylglucosaminyltransferases; D018091:Receptors, AMPA; C449880:O-GlcNAc transferase; C104722:glutamate receptor ionotropic, AMPA 2