4.8 Article

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

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.0703805104

关键词

dorsal root ganglia neurons

资金

  1. NIDA NIH HHS [R01 DA000564, DA11806, K05-DA70554, K05 DA070554, R01 DA011190, K02 DA13926, P50 DA011806, DA01583, DA00564, R56 DA000564, DA11190, R01 DA001583, K02 DA013926] Funding Source: Medline
  2. NIDDK NIH HHS [DK60521, R01 DK054733, DK54733, R01 DK060521] Funding Source: Medline

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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.

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