Prostaglandin E-2 Promotes Na(v)1.8 Trafficking via Its Intracellular RRR Motif Through the Protein Kinase A Pathway
文献类型：期刊论文
| 作者 | Liu, C; Li, Q; Su, YY; Bao, L |
| 刊名 | TRAFFIC
 |
| 出版日期 | 2010 |
| 卷号 | 11期号:3页码:405-417 |
| 关键词 | dorsal root ganglion inflammatory pain Na(v)1 8 patch clamp prostaglandin E-2 protein kinase A trafficking voltage-gated sodium channel |
| 通讯作者 | Bao, L (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,baolan@sibs.ac.cn |
| 英文摘要 | Voltage-gated sodium channels (Na-v) are essential for the initiation and propagation of action potentials in neurons. Na(v)1.8 activity is regulated by prostaglandin E-2 (PGE(2)). There is, however, no direct evidence showing the regulated trafficking of Na(v)1.8, and the molecular and cellular mechanism of PGE(2)-induced sodium channel trafficking is not clear. Here, we report that PGE(2) regulates the trafficking of Na(v)1.8 through the protein kinase A (PKA) signaling pathway, and an RRR motif in the first intracellular loop of Na(v)1.8 mediates this effect. In rat dorsal root ganglion (DRG) neurons, prolonged PGE(2) treatment enhanced Na(v)1.8 currents by increasing the channel density on the cell surface. Activation of PKA by forskolin had the same effect on DRG neurons and human embryonic kidney 293T cells expressing Na(v)1.8. Inhibition of PKA completely blocked the PGE(2)-promoted effect on Na(v)1.8. Mutation of five PKA phosphorylation sites or the RRR motif in the first intracellular loop of Na(v)1.8 abolished the PKA-promoted Na(v)1.8 surface expression. Furthermore, a membrane-tethered peptide containing the intracellular RRR motif disrupted the PGE(2)-induced promotion of the Na(v)1.8 current in DRG neurons. Our data indicate that PGE(2) promotes the surface expression of Na(v)1.8 via an intracellular RRR motif, and provide a novel mechanism for functional modulation of Na(v)1.8 by hyperalgesic agents. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | RESISTANT SODIUM-CHANNEL ; CAMP-DEPENDENT PHOSPHORYLATION ; RAT SENSORY NEURONS ; TETRODOTOXIN-RESISTANT ; INFLAMMATORY PAIN ; DRG NEURONS ; NEUROPATHIC PAIN ; CURRENT-DENSITY ; ER RETENTION ; NA+ CURRENT |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000274454500009 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/981]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Liu, C,Li, Q,Su, YY,et al. Prostaglandin E-2 Promotes Na(v)1.8 Trafficking via Its Intracellular RRR Motif Through the Protein Kinase A Pathway[J]. TRAFFIC,2010,11(3):405-417. |
| APA | Liu, C,Li, Q,Su, YY,&Bao, L.(2010).Prostaglandin E-2 Promotes Na(v)1.8 Trafficking via Its Intracellular RRR Motif Through the Protein Kinase A Pathway.TRAFFIC,11(3),405-417. |
| MLA | Liu, C,et al."Prostaglandin E-2 Promotes Na(v)1.8 Trafficking via Its Intracellular RRR Motif Through the Protein Kinase A Pathway".TRAFFIC 11.3(2010):405-417. |
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