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学科主题: 基础医学
题名:
Functional Rescue of Kv4.3 Channel Tetramerization Mutants by KChIP4a
作者: Liang, Ping; Chen, Hao; Cui, Yuanyuan; Lei, Lei; Wang, KeWei
刊名: BIOPHYSICAL JOURNAL
发表日期: 2010-06-16
DOI: 10.1016/j.bpj.2010.03.044
卷: 98, 期:12, 页:2867-2876
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biophysics
研究领域[WOS]: Biophysics
关键词[WOS]: INTRACELLULAR T1-T1 INTERFACE ; POTASSIUM CHANNEL ; K+ CHANNEL ; KV CHANNEL ; 3-DIMENSIONAL STRUCTURE ; INTERACTING PROTEINS ; PYRAMIDAL NEURONS ; I-TO ; TRAFFICKING ; EXPRESSION
英文摘要:

KChIP4a shows a high homology with other members of the family of Kv channel-interacting proteins (KChIPs) in the conserved C-terminal core region, but exhibits a unique modulation of Kv4 channel gating and surface expression. Unlike KChIP1, the KChIP4 splice variant KChIP4a has been shown to inhibit surface expression and function as a suppressor of channel inactivation of Kv4. In this study, we sought to determine whether the multitasking KChIP4a modulates Kv4 function in a clamping fashion similar to that shown by KChIP1. Injection of Kv4.3 T1 zinc mutants into Xenopus oocytes resulted in the nonfunctional expression of Kv4.3 channels. Coexpression of Kv4.3 zinc mutants with WT KChIP4a gave rise to the functional expression of Kv4.3 current. Oocyte surface labeling results confirm the correlation between functional rescue and enhanced surface expression of zinc mutant proteins. Chimeric mutations that replace the Kv4.3 N-terminus with N-terminal KChIP4a or N-terminal deletion of KChIP4a further demonstrate that the functional rescue of Kv4.3 channel tetramerization mutants depends on the KChIP4a core region, but not its N-terminus. Structure-guided mutation of two critical residues of core KChIP4a attenuated functional rescue and tetrameric assembly. Moreover, size exclusion chromatography combined with fast protein liquid chromatography showed that KChIP4a can drive zinc mutant monomers to assemble as tetramers. Taken together, our results show that KChIP4a can rescue the function of tetramerization-defective Kv4 monomers. Therefore, we propose that core KChIP4a functions to promote tetrameric assembly and enhance surface expression of Kv4 channels by a clamping action, whereas its N-terminus inhibits surface expression of Kv4 by a mechanism that remains elusive.

语种: 英语
所属项目编号: 30630017 ; 2006AA02Z183 ; 2007CB512100 ; 706002
项目资助者: National Science Foundation of China ; Ministry of Science Technology of China ; Ministry of Education of China
WOS记录号: WOS:000278913500015
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51962
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Dept Neurobiol, Beijing 100871, Peoples R China

Recommended Citation:
Liang, Ping,Chen, Hao,Cui, Yuanyuan,et al. Functional Rescue of Kv4.3 Channel Tetramerization Mutants by KChIP4a[J]. BIOPHYSICAL JOURNAL,2010,98(12):2867-2876.
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