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The Journal of Neuroscience, September 20, 2006, 26(38):9743-9749; doi:10.1523/JNEUROSCI.3014-06.2006

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Cellular/Molecular
Netrin-1 Signaling Regulates De Novo Protein Synthesis of {kappa} Opioid Receptor by Facilitating Polysomal Partition of Its mRNA

Nien-Pei Tsai, Jing Bi, Horace H. Loh, and Li-Na Wei

Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Correspondence should be addressed to Li-Na Wei, Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455. Email: weixx009{at}umn.edu

The expression of {kappa} opioid receptor (KOR) is subjected to both transcriptional and posttranscriptional controls. We report that KOR translation is regulated by netrin-1 in primary neurons of dorsal root ganglion (DRG) and in P19 embryonal carcinoma cells. Without stimulation, a significant portion of KOR mRNA is maintained in a dormant state and partitions in the translationally inactive, post-polysomal fraction. During netrin-1 stimulation, which activates its downstream target focal adhesion kinase (FAK), KOR mRNA rapidly partitions to the translationally active polysomal fraction. Functionally, the newly synthesized KOR proteins in DRG neurons are able to bind to specific ligands. This report describes the first example of netrin-1 signaling in the translational control of a drug receptor KOR, which involves the mediator of netrin-1, FAK, and a novel mechanism that enhances the association of target mRNA with polysomes for translational activation.

Key words: {kappa} opioid receptor; netrin-1; FAK; translational regulation; dorsal root ganglia neuron; polysomal partition

Received May 2, 2006; revised Aug. 7, 2006; accepted Aug. 10, 2006.

Correspondence should be addressed to Li-Na Wei, Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455. Email: weixx009{at}umn.edu




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Bi, N.-P. Tsai, H.-Y. Lu, H. H. Loh, and L.-N. Wei
Copb1-facilitated axonal transport and translation of {kappa} opioid-receptor mRNA
PNAS, August 21, 2007; 104(34): 13810 - 13815.
[Abstract] [Full Text] [PDF]


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