Copb1-facilitated axonal transport and translation of κ opioid-receptor mRNA

Copb1-facilitated axonal transport and translation of κ opioid-receptor mRNA
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DOI:
10.1073/pnas.0703805104
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发表时间:
2007-08-21
影响因子:
11.1
通讯作者:
Wei, Li-Na
Wei, Li-Na
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bi, Jing;Tsai, Nien-Pei;Wei, Li-Na

文献摘要

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K 阿片受体 (KOR) 的 mRNA 可转运至神经纤维,包括背根神经节 (DRG) 的轴突,并可进行局部翻译。酵母三杂交筛选将 Copb1 鉴定为 kor mRNA 相关蛋白,它与内源性 kor mRNA 形成复合物,内源性 kor mRNA 共定位于 DRG 神经元的体细胞和轴突中。通过观察 Campenot 室中生物素标记的 kor mRNA 的动员,直接证明 kor mRNA 的轴突转运。 kor mRNA 有效转运到侧室需要 Copb1,并且可以被破坏微管的药物阻断。通过使用 MS2-GFP mRNA 标记系统确认了 Copb1 在动员 kor mRNA 中的要求。此外,Copb1 还促进体细胞和轴突中 kor mRNA 的翻译。这项研究为微管依赖性、活跃的轴突 kor mRNA 转运过程提供了证据,该过程涉及 Copb1,并且可以刺激局部翻译,并表明运往轴突等偏远区域的 mRNA 的转运和翻译之间存在耦合。
mRNA of K opioid receptor (KOR) can be transported to nerve fibers, including axons of dorsal root ganglia (DRG), and can be locally translated. Yeast three-hybrid screening identifies Copb1 as a kor mRNA-associated protein that form complexes with endogenous kor mRNA, which are colocalized in the soma and axons of DRG neurons. Axonal transport of kor mRNA is demonstrated, directly, by observing mobilization of biotin-labeled kor mRNA in Campenot chambers. Efficient transport of kor mRNA into the side chamber requires Copb1 and can be blocked by a drug that disrupts microtubules. The requirement for Copb1 in mobilizing kor mRNA is confirmed by using the MS2-GFP mRNA-tagging system. Furthermore, Copb1 also facilitates the translation of kor mRNA in the soma and axons. This study provides evidence for a microtubule dependent, active axonal kor mRNA-transport process that involves Copb1 and can stimulate localized translation and suggests coupling of transport and translation of mRNAs destined to the remote areas such as axons.