Netrin-1 Signaling Regulates<i>De Novo</i>Protein Synthesis of κ Opioid Receptor by Facilitating Polysomal Partition of Its mRNA

Tsai, Nien Pei; Bi, Jing; Loh, Horace H.; Li, Wei

doi:10.1523/jneurosci.3014-06.2006

Cited by 38 publications

(42 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, we have found that most kor mRNA is repressed until it is stimulated for translation (11,34). It has also been suggested that mRNAs, during transport, are usually silenced by repressors (35)(36)(37).…”

Section: Discussionmentioning

confidence: 89%

See 1 more Smart Citation

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

Tsai

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

mRNA of 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 microtubuledependent, 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.dorsal root ganglia neurons T hree major opioid receptor types, , ␦, and , are known (1, 2), each interacting with specific ligands to modulate pain sensation, consciousness, and autonomic functions. Pharmacological studies have demonstrated the significance of the number (3) of opioid receptors and their subcellular distribution (4-7) in the manifestation of opioid drugs. Studies of gene regulation have revealed that although transcriptional regulation is critical for cells to express opioid receptor mRNAs (8), these mRNAs are mostly silent and require extensive posttranscriptional regulation for the ultimate production of these proteins (9). Using the opioid receptor (KOR) as a model, we have begun to uncover several posttranscriptional regulatory events important for the expression of KOR protein. These include alternative mRNA splicing, changing mRNA stability (10), localized translation (11), and mRNA transport (12, 13) in neurons.

show abstract

Section: Discussionmentioning

confidence: 89%

“…Using the opioid receptor (KOR) as a model, we have begun to uncover several posttranscriptional regulatory events important for the expression of KOR protein. These include alternative mRNA splicing, changing mRNA stability (10), localized translation (11), and mRNA transport (12,13) in neurons.…”

mentioning

confidence: 99%

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

Tsai

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…All of these putative target mRNAs have been identified in the axons of invertebrates (Martin 2004;Crispino et al 2009) and vertebrates (Willis et al 2007;Taylor et al 2009;Vogelaar et al 2009). It is important to note that receptors and transmembrane proteins can be synthesized locally in axons (Spencer et al 2000;Bi et al 2006;Tsai et al 2006) and that functional receptors appear to be incorporated into the axolemma via an ER-and Golgi-dependent mechanism (Merianda et al 2009). Although attention has been focused on miRNAs that are relatively abundant or enriched in the axon in this report (Table 1), it is likely that low abundance miRNAs might also play an important role in the regulation of local translation and axonal function.…”

Section: Resultsmentioning

confidence: 99%

Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons

Natera-Naranjo¹,

Aschrafi²,

Gioio³

et al. 2010

RNA

169

163

View full text Add to dashboard Cite

microRNAs (miRNAs) constitute a novel class of small, noncoding RNAs that act as negative post-transcriptional regulators of gene expression. Although the nervous system is a prominent site of miRNA expression, little is known about the spatial expression profiles of miRNAs in neurons. Here, we employed compartmentalized Campenot cell culture chambers to obtain a pure axonal RNA fraction of superior cervical ganglia (SCG) neurons, and determined the miRNA expression levels in these subcellular structural domains by microarray analysis and by real-time reverse-transcription polymerase chain reaction. The data revealed stable expression of a number of mature miRNAs that were enriched in the axons and presynaptic nerve terminals. Among the 130 miRNAs identified in the axon, miR-15b, miR-16, miR-204, and miR-221 were found to be highly abundant in distal axons as compared with the cell bodies of primary sympathetic neurons. Moreover, a number of miRNAs encoded by a common primary transcript (pri-miRNA) were differentially expressed in the distal axons, suggesting that there is a differential subcellular transport of miRNAs derived from the same coding region of the genome. Taken together, the data provide an important resource for future studies on the regulation of axonal protein synthesis and the role played by miRNAs in the maintenance of axonal structure and function as well as neuronal growth and development.

show abstract

“…important switch to activate the silenced KOR mRNA for translation is the phosphorylation of Grb7 by Focal Adhesion Kinase (FAK), which is a downstream signal mediator for various growth factors such as Netrin and EGF (13)(14)(15). To determine the physiological function of KOR in the developing nervous system, we conducted preliminary experiments using primary DRG neurons dissected from the wild-type (WT) and KOR-null animals (16) to examine several developmental parameters and the sensitivity of the dissected DRG cultures to stimulation by potential growth factors.…”

mentioning

confidence: 99%

“…P19 cells and DRG neurons were cultured as described in ref. 13, with slight modification. To exclude extrinsic effects on KOR expression and axon extension, NGF and N2 supplements were excluded from the regular culture medium.…”

mentioning

confidence: 99%

Kappa opioid receptor contributes to EGF-stimulated neurite extension in development

Tsai

Tsui

Pintar

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Epidermal growth factor (EGF), a mitogen, also stimulates neurite extension during development, but the underlying mechanism is elusive. This study reveals a functional role for kappa opioid receptor (KOR) in EGF-stimulated neurite extension, and the underlying mechanism. EGF and activated EGF receptor (EGFR) levels are elevated in embryonic spinal cords during late gestation stages, with concurrent rise in protein levels of KOR and axon extension markers, growth-associated protein 43 (GAP43), and transient axonal glycoprotein-1 (TAG-1). Both GAP43 and TAG-1 levels are significantly lower in KOR-null (KOR −/− ) spinal cords, and EGFR inhibitors effectively reduce the levels of KOR, GAP43, and TAG-1 in wildtype embryonic spinal cords. For KOR −/− or KOR-knockdown dorsal root ganglion (DRG) neurons, EGF can no longer effectively stimulate axon extension, which can be rescued by introducing a constitutive KOR expressing vector but not by a regulated KOR vector carrying its 5′ untranslated region, which can be bound and repressed by growth factor receptor-bound protein 7 (Grb7). Furthermore, blocking KOR activation by application of anti-dynorphin, KOR antagonist, or EGFR inhibitor effectively reduces axon extension of DRG neurons. Thus, EGF-stimulated axon extension during development is mediated, at least partially, by specific elevation of KOR protein production at posttranscriptional level, as well as activation of KOR signaling. The result also reveals an action of EGF to augment posttranscriptional regulation of certain mRNAs during developmental stages.5′ untranslated region | dorsal root ganglion | epidermal growth factor | growth factor receptor-bound protein 7 | posttranscriptional regulation

show abstract

Netrin-1 Signaling RegulatesDe NovoProtein Synthesis of κ Opioid Receptor by Facilitating Polysomal Partition of Its mRNA

Cited by 38 publications

References 28 publications

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

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

Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons

Kappa opioid receptor contributes to EGF-stimulated neurite extension in development

Contact Info

Product

Resources

About