Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression

被引:256
作者
Chung, HJ
Steinberg, JP
Huganir, RL
Linden, DJ
机构
[1] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA
关键词
D O I
10.1126/science.1082915
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1751 / 1755
页数:5
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