MRC Centre for Synaptic Plasticity, School of Biochemistry, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
Biochem Biophys Res Commun. 2011 Jun 17;409(4):657-62. doi: 10.1016/j.bbrc.2011.05.060. Epub 2011 May 17.
G-protein coupled receptor interacting scaffold protein (GISP) is a multi-domain, brain-specific protein derived from the A-kinase anchoring protein (AKAP)-9 gene. Using yeast two-hybrid screens to identify GISP interacting proteins we isolated the SUMO conjugating enzyme Ubc9. GISP interacts with Ubc9 in vitro, in heterologous cells and in neurons. SUMOylation is a post-translational modification in which the small protein SUMO is covalently conjugated to target proteins, modulating their function. Consistent with its interaction with Ubc9, we show that GISP is SUMOylated by both SUMO-1 and SUMO-2 in both in vitro SUMOylation assays and in mammalian cells. Intriguingly, SUMOylation of GISP in neurons occurs in an activity-dependent manner in response to chemical LTP. These data suggest that GISP is a novel neuronal SUMO substrate whose SUMOylation status is modulated by neuronal activity.
G 蛋白偶联受体相互作用支架蛋白（GISP）是一种多结构域、脑特异性蛋白，来源于蛋白激酶锚定蛋白（AKAP）-9 基因。通过酵母双杂交筛选来鉴定 GISP 相互作用蛋白，我们分离出 SUMO 连接酶 Ubc9。GISP 在体外、异源细胞和神经元中与 Ubc9 相互作用。SUMO 化是一种翻译后修饰，其中小分子蛋白 SUMO 通过共价键与靶蛋白结合，调节其功能。与它与 Ubc9 的相互作用一致，我们表明 GISP 可被 SUMO-1 和 SUMO-2 在体外 SUMO 化测定和哺乳动物细胞中进行 SUMO 化。有趣的是，神经元中 GISP 的 SUMO 化以活性依赖的方式发生，以响应化学性长时程增强。这些数据表明 GISP 是一种新型的神经元 SUMO 底物，其 SUMO 化状态受神经元活动的调节。
