IR@PKUHSC  > 北京大学基础医学院  > 神经生物学系
学科主题基础医学
Cyclin-Dependent Kinase 5 Controls TRPV1 Membrane Trafficking and the Heat Sensitivity of Nociceptors through KIF13B
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
2012-10-17
DOI10.1523/JNEUROSCI.1634-12.2012
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
WOS记录号WOS:000310054000024
项目编号30830044 ; 30925015 ; 81161120497 ; 7092061 ; 200800011028 ; 20060001121
资助机构National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Specialized Research Fund for Doctoral Programs of Higher Education
引用统计
被引频次:44[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/400002259/64766
专题北京大学基础医学院_神经生物学系
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
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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.
APA Xing, Bao-Ming.,Yang, Yan-Rui.,Du, Jun-Xia.,Chen, Hai-Jing.,Qi, Cai.,...&Wang, Yun.(2012).Cyclin-Dependent Kinase 5 Controls TRPV1 Membrane Trafficking and the Heat Sensitivity of Nociceptors through KIF13B.JOURNAL OF NEUROSCIENCE,32(42),14709-14721.
MLA Xing, Bao-Ming,et al."Cyclin-Dependent Kinase 5 Controls TRPV1 Membrane Trafficking and the Heat Sensitivity of Nociceptors through KIF13B".JOURNAL OF NEUROSCIENCE 32.42(2012):14709-14721.
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