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学科主题基础医学
Functional Rescue of Kv4.3 Channel Tetramerization Mutants by KChIP4a
Liang, Ping; Chen, Hao; Cui, Yuanyuan; Lei, Lei; Wang, KeWei
刊名BIOPHYSICAL JOURNAL
2010-06-16
DOI10.1016/j.bpj.2010.03.044
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
WOS记录号WOS:000278913500015
项目编号30630017 ; 2006AA02Z183 ; 2007CB512100 ; 706002
资助机构National Science Foundation of China ; Ministry of Science Technology of China ; Ministry of Education of China
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51962
专题北京大学基础医学院_神经生物学系
北京大学基础医学院
北京大学药学院_分子与细胞药理学系
北京大学临床肿瘤学院_肝胆胰外二科
北京大学临床肿瘤学院_妇科肿瘤科
作者单位Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Dept Neurobiol, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
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.
APA Liang, Ping,Chen, Hao,Cui, Yuanyuan,Lei, Lei,&Wang, KeWei.(2010).Functional Rescue of Kv4.3 Channel Tetramerization Mutants by KChIP4a.BIOPHYSICAL JOURNAL,98(12),2867-2876.
MLA Liang, Ping,et al."Functional Rescue of Kv4.3 Channel Tetramerization Mutants by KChIP4a".BIOPHYSICAL JOURNAL 98.12(2010):2867-2876.
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