北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 神经生物学系  > 期刊论文
学科主题: 基础医学
题名:
Cyclin-Dependent Kinase 5 Controls TRPV1 Membrane Trafficking and the Heat Sensitivity of Nociceptors through KIF13B
作者: Xing, Bao-Ming1,2; Yang, Yan-Rui3; Du, Jun-Xia1,2; Chen, Hai-Jing1,2; Qi, Cai1,2; Huang, Zhi-Hua4; Zhang, Ying1,2; Wang, Yun1,2
刊名: JOURNAL OF NEUROSCIENCE
发表日期: 2012-10-17
DOI: 10.1523/JNEUROSCI.1634-12.2012
卷: 32, 期:42, 页:14709-14721
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: PRIMARY SENSORY NEURONS ; ACTIVATED ION-CHANNEL ; ROOT GANGLION NEURONS ; CAPSAICIN RECEPTOR ; FHA DOMAIN ; CELL-LINE ; PROTEIN ; PHOSPHORYLATION ; HYPERALGESIA ; TRANSPORT
英文摘要:

The number of functional transient receptor potential vanilloid 1 (TRPV1) channels at the surface, especially at the peripheral terminals of primary sensory neurons, regulates heat sensitivity, and increased surface localization of TRPV1s contributes to heat hyperalgesia. However, the mechanisms for regulating TRPV1 surface localization are essentially unknown. Here, we show that cyclin-dependent kinase 5 (Cdk5), a new player in thermal pain sensation, positively regulates TRPV1 surface localization. Active Cdk5 was found to promote TRPV1 anterograde transport in vivo, suggesting a regulatory role of Cdk5 in TRPV1 membrane trafficking. TRPV1-containing vesicles bind to the forkhead-associated (FHA) domain of the KIF13B (kinesin-3 family member 13B) and are thus delivered to the cell surface. Overexpression of Cdk5 or its activator p35 promoted and inhibition of Cdk5 activity prevented the KIF13B-TRPV1 association, indicating that Cdk5 promotes TRPV1 anterograde transport by mediating the motor-cargo association. Cdk5 phosphorylates KIF13B at Thr-506, a residue located in the FHA domain. T506A mutation reduced the motor-cargo interaction and the cell-permeable TAT-T506 peptide, targeting to the Thr-506, decreased TRPV1 surface localization, demonstrating the essential role of Thr-506 phosphorylation in TRPV1 transport. Moreover, complete Freund′s adjuvant (CFA) injection-induced activation of Cdk5 increased the anterograde transport of TRPV1s, contributing to the development and possibly the maintenance of heat hyperalgesia, whereas intrathecal delivery of the TAT-T506 peptide alleviated CFA-induced heat hyperalgesia in rats. Thus, Cdk5 regulation of TRPV1 membrane trafficking is a fundamental mechanism controlling the heat sensitivity of nociceptors, and moderate inhibition of Thr-506 phosphorylation during inflammation might be helpful for the treatment of inflammatory thermal pain.

语种: 英语
所属项目编号: 30830044 ; 30925015 ; 81161120497 ; 7092061 ; 200800011028 ; 20060001121
项目资助者: National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Specialized Research Fund for Doctoral Programs of Higher Education
WOS记录号: WOS:000310054000024
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64766
Appears in Collections:基础医学院_神经生物学系_期刊论文

Files in This Item:
File Name/ File Size Content Type Version Access License
Cyclin-Dependent Kinase 5 Controls TRPV1 Membrane Trafficking and the Heat Sensitivity of Nociceptors through KIF13B.pdf(2868KB)期刊论文出版稿限制开放 联系获取全文

作者单位: 1.Peking Univ, Neurosci Res Inst, Hlth Sci Ctr, Beijing 100191, Peoples R China
2.Peking Univ, Dept Neurobiol, Key Lab Neurosci, Minist Educ & Hlth,Hlth Sci Ctr, Beijing 100191, Peoples R China
3.Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol & Dev Biol, Beijing 100101, Peoples R China
4.Gannan Med Coll, Ganzhou 341000, Jiangxi, Peoples R China

Recommended Citation:
Xing, Bao-Ming,Yang, Yan-Rui,Du, Jun-Xia,et al. Cyclin-Dependent Kinase 5 Controls TRPV1 Membrane Trafficking and the Heat Sensitivity of Nociceptors through KIF13B[J]. JOURNAL OF NEUROSCIENCE,2012,32(42):14709-14721.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Xing, Bao-Ming]'s Articles
[Yang, Yan-Rui]'s Articles
[Du, Jun-Xia]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Xing, Bao-Ming]‘s Articles
[Yang, Yan-Rui]‘s Articles
[Du, Jun-Xia]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace