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学科主题: 基础医学
题名:
Identification of a Tetrameric Assembly Domain in the C Terminus of Heat-activated TRPV1 Channels
作者: Zhang, Feng1; Liu, Shuang1; Yang, Fan3; Zheng, Jie3; Wang, KeWei1,2
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2011-04-29
DOI: 10.1074/jbc.M111.223941
卷: 286, 期:17, 页:15308-15316
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: ANKYRIN REPEAT DOMAIN ; CAPSAICIN RECEPTOR ; ION-CHANNEL ; VANILLOID RECEPTOR-1 ; PHOSPHORYLATION ; DETERMINANT ; SENSITIVITY ; SUBUNITS
英文摘要:

Transient receptor potential (TRP) channels as cellular sensors are thought to function as tetramers. Yet, the molecular determinants governing channel multimerization remain largely elusive. Here we report the identification of a segment comprising 21 amino acids (residues 752-772 of mouse TRPV1) after the known TRP-like domain in the channel C terminus that functions as a tetrameric assembly domain (TAD). Purified recombinant C-terminal proteins of TRPV1-4, but not the N terminus, mediated the protein-protein interaction in an in vitro pulldown assay. Western blot analysis combined with electrophysiology and calcium imaging demonstrated that TAD exerted a robust dominant-negative effect on wild-type TRPV1. When fused with the membrane-tethered peptide Gap43, the TAD blocked the formation of stable homomultimers. Calcium imaging and current recordings showed that deletion of the TAD in a poreless TRPV1 mutant subunit suppressed its dominant-negative phenotype, confirming the involvement of the TAD in assembly of functional channels. Our findings suggest that the C-terminal TAD in TRPV1 channels functions as a domain that is conserved among TRPV1-4 and mediates a direct subunit-subunit interaction for tetrameric assembly.

语种: 英语
所属项目编号: 30630017 ; 30970919 ; 2007CB512100 ; B07001
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:000289788300062
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65294
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: 1.Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Neurosci Res Inst, Beijing 100191, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Dept Mol & Cellular Pharmacol, Beijing 100191, Peoples R China
3.Univ Calif Davis, Dept Physiol & Membrane Biol, Davis, CA 95616 USA

Recommended Citation:
Zhang, Feng,Liu, Shuang,Yang, Fan,et al. Identification of a Tetrameric Assembly Domain in the C Terminus of Heat-activated TRPV1 Channels[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(17):15308-15316.
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