Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Neurochem Res. 2010 May;35(5):782-8. doi: 10.1007/s11064-010-0135-1. Epub 2010 Feb 18.
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.
本研究探讨了 O-连接β-N-乙酰氨基葡萄糖（O-GlcNAc）糖基化（O-GlcNAcylation）在 AMPA 受体转运中的作用。O-GlcNAc 转移酶抑制剂别嘌呤醇增强了在非洲爪蟾卵母细胞中表达的由 GluR1 亚基组成的 AMPA 受体的反应。具有缺乏 CaMKII 磷酸化位点的突变 GluR1（S831A）受体的别嘌呤醇没有增强作用。别嘌呤醇促进基础突触传递至基础水平的约 120%，并增强大鼠海马切片中的 Schaffer 侧枝-CA1 长时程增强（LTP），特别是在 LTP 的后期。别嘌呤醇刺激大鼠海马切片中 GluR1 和 GluR2 亚基从细胞质向质膜的易位，尽管它对 NR1 亚基的亚细胞分布没有影响。总之，本研究的结果表明，别嘌呤醇通过抑制 O-GlcNAcylation 来调节 AMPA 受体转运，从而调节海马突触传递和突触可塑性。
