School of Biochemistry, University of Bristol, Bristol, United Kingdom.
PLoS One. 2013;8(1):e52345. doi: 10.1371/journal.pone.0052345. Epub 2013 Jan 11.
Multiple pathways participate in the AMPA receptor trafficking that underlies long-term potentiation (LTP) of synaptic transmission. Here we demonstrate that protein SUMOylation is required for insertion of the GluA1 AMPAR subunit following transient glycine-evoked increase in AMPA receptor surface expression (ChemLTP) in dispersed neuronal cultures. ChemLTP increases co-localisation of SUMO-1 and the SUMO conjugating enzyme Ubc9 and with PSD95 consistent with the recruitment of SUMOylated proteins to dendritic spines. In addition, we show that ChemLTP increases dendritic levels of SUMO-1 and Ubc9 mRNA. Consistent with activity dependent translocation of these mRNAs to sites near synapses, levels of the mRNA binding and dendritic transport protein CPEB are also increased by ChemLTP. Importantly, reducing the extent of substrate protein SUMOylation by overexpressing the deSUMOylating enzyme SENP-1 or inhibiting SUMOylation by expressing dominant negative Ubc9 prevent the ChemLTP-induced increase in both AMPAR surface expression and dendritic SUMO-1 mRNA. Taken together these data demonstrate that SUMOylation of synaptic protein(s) involved in AMPA receptor trafficking is necessary for activity-dependent increases in AMPAR surface expression.
多种途径参与 AMPA 受体转运，而这种转运是突触传递长时程增强（LTP）的基础。在这里，我们证明了在分散神经元培养物中，短暂甘氨酸诱导的 AMPA 受体表面表达增加（ChemLTP）后，GluA1 AMPAR 亚基的插入需要蛋白质 SUMO 化。ChemLTP 增加了 SUMO-1 和 SUMO 连接酶 Ubc9 与 PSD95 的共定位，与 SUMO 化蛋白向树突棘的募集一致。此外，我们还表明，ChemLTP 增加了树突状 SUMO-1 和 Ubc9 mRNA 的水平。与这些 mRNA 依赖活性向突触附近部位转运一致，ChemLTP 还增加了 mRNA 结合和树突运输蛋白 CPEB 的水平。重要的是，通过过表达去 SUMO 化酶 SENP-1 或表达显性负 Ubc9 来减少底物蛋白 SUMO 化的程度，可防止 ChemLTP 诱导的 AMPAR 表面表达和树突状 SUMO-1 mRNA 的增加。这些数据表明，参与 AMPA 受体转运的突触蛋白的 SUMO 化对于活性依赖性 AMPAR 表面表达增加是必要的。
