文章基本信息

标题：Activity-dependent NMDA receptor degradation mediated by retrotranslocation and ubiquitination
本地全文：下载
作者：Akihiko Kato ; Nathalie Rouach ; Roger A. Nicoll 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：15
页码：5600-5605
DOI：10.1073/pnas.0501769102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The extracellular N-terminal domain (NTD) is the largest region of NMDA receptors; however, biological roles for this ectodomain remain unknown. Here, we determined that the F-box protein, Fbx2, bound to high-mannose glycans of the NR1 ectodomain. F-box proteins specify ubiquitination by linking protein substrates to the terminal E3 ligase. Indeed, ubiquitination of NR1 was increased by Fbx2 and diminished by an Fbx2 dominant-negative mutant. When expressed in hippocampal neurons, this Fbx2 dominant-negative mutant augmented NR1 subunit levels and NMDA receptor-mediated currents in an activity-dependent fashion. These results suggest that homeostatic control of synaptic NR1 involves receptor retrotranslocation and degradation by the ubiquitin-proteasome pathway.
关键词：endoplasmic reticulum degradation pathway ; neuronal activity ; NFB42 ; proteasome ; ubiquitylation