Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression
Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression
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DOI：
10.1126/science.1082915
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发表时间：
2003-06-13
期刊：
影响因子：
56.9
通讯作者：
Linden, DJ
中科院分区：
文献类型：
--
作者：
Chung, HJ;Steinberg, JP;Linden, DJ
小脑长时程抑制（LTD）是一种突触记忆模型，需要蛋白激酶C（PKC）激活，表现为突触后α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）受体数量减少。LTD是不存在的突变小鼠缺乏AMPA受体GluR 2亚基的小脑浦肯野细胞培养，可以通过瞬时转染野生型GluR 2亚基获救。转染一个点突变体，消除PKC磷酸化的Ser（880）在羧基端PDZ配体的GluR 2未能恢复LTD。相反，转染一个点突变体，模仿磷酸化的Ser（880）闭塞随后LTD。因此，PKC磷酸化的GluR 2 Ser（880）是一个关键事件在小脑LTD的诱导。
Cerebellar long-term depression (LTD) is a model of synaptic memory that requires protein kinase C (PKC) activation and is expressed as a reduction in the number of postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate ( AMPA) receptors. LTD was absent in cultured cerebellar Purkinje cells from mutant mice lacking the AMPA receptor GluR2 subunit and could be rescued by transient transfection with the wild-type GluR2 subunit. Transfection with a point mutant that eliminated PKC phosphorylation of Ser(880) in the carboxyterminal PDZ ligand of GluR2 failed to restore LTD. In contrast, transfection with a point mutant that mimicked phosphorylation at Ser(880) occluded subsequent LTD. Thus, PKC phosphorylation of GluR2 Ser(880) is a critical event in the induction of cerebellar LTD.