Abstract
The present study investigated the role of O-linked β-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.
Similar content being viewed by others
References
Kelly WG, Dahmus ME, Hart GW (1993) RNA polymerase II is a glycoprotein. Modification of the COOH-terminal domain by O-GlcNAc. J Biol Chem 268:10416–10424
Slawson C, Hart GW (2003) Dynamic interplay between O-GlcNAc and O-phosphate: the sweet side of protein regulation. Curr Opin Struct Biol 13:631–636
Zhang F, Su K, Yang X, Bowe DB, Paterson AJ, Kudlow JE (2003) O-GlcNAc modification is an endogenous inhibitor of the proteasome. Cell 115:715–725
Whelan SA, Hart GW (2003) Proteomic approaches to analyze the dynamic relationships between nucleocytoplasmic protein glycosylation and phosphorylation. Circ Res 93:1047–1058
Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103–126
Bredt DS, Nicoll RA (2003) AMPA receptor trafficking at excitatory synapses. Neuron 40:361–379
Seidenman KJ, Steinberg JP, Huganir R, Malinow R (2003) Glutamate receptor subunit 2 Serine 880 phosphorylation modulates synaptic transmission and mediates plasticity in CA1 pyramidal cells. J Neurosci 23:9220–9228
Lu W, Ziff EB (2005) PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron 47:407–421
Konrad RJ, Zhang F, Hale JE, Knierman MD, Becker GW, Kudlow JE (2002) Alloxan is an inhibitor of the enzyme O-linked N-acetylglucosamine transferase. Biochem Biophys Res Commun 293:207–212
Barria A, Derkach V, Soderling T (1997) Identification of the Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-type glutamate receptor. J Biol Chem 272:32727–32730
Low SH, Chapin SJ, Weimbs T, Komuves LG, Bennett MK, Mostov KE (1996) Differential localization of syntaxin isoforms in polarized Madin-Darby canine kidney cells. Mol Biol Cell 7:2007–2018
Wenthold RJ, Petralia RS, Blahos JII, Niedzielski AS (1996) Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons. J Neurosci 16:1982–1989
Collingridge GL, Isaac JT, Wang YT (2004) Receptor trafficking and synaptic plasticity. Nat Rev Neurosci 5:952–962
Shi SH, Hayashi Y, Petralia RS, Zaman SH, Wenthold RJ, Svoboda K, Malinow R (1999) Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284:1811–1816
Soderling TR, Derkach VA (2000) Postsynaptic protein phosphorylation and LTP. Trends Neurosci 23:75–80
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kanno, T., Yaguchi, T., Nagata, T. et al. Regulation of AMPA Receptor Trafficking by O-Glycosylation. Neurochem Res 35, 782–788 (2010). https://doi.org/10.1007/s11064-010-0135-1
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-010-0135-1