The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation

Tsai, Nien Pei; Bi, Jing; Wei, Li‐Na

doi:10.1038/sj.emboj.7601598

Cited by 51 publications

(81 citation statements)

References 33 publications

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“…This confirmed that Grb7 was required for elevating KOR level. However, this outcome seemed to contradict its previously established role as a KOR translational repressor (14). A potential explanation was that Grb7 could also regulate other posttranscriptional regulatory events through its binding to KOR mRNA, such as mobilizing KOR mRNA, in addition to its repressing KOR translation.…”

Section: Signal Of Egf To Stimulate Kor/dynorphin-dependent Axon Extecontrasting

confidence: 41%

“…The dominant negative mutant Grb7 would remain tightly binding to KOR mRNA, thereby ultimately arresting KOR mRNA translation. In the presence of this dominant negative mutant Grb7 that tightly bound KOR 5′-UTR and could not release KOR mRNA for translation (14), the 5-UTR-carrying KOR vector would be resistant to EGF stimulation. Indeed, as shown in Fig.…”

Section: Signal Of Egf To Stimulate Kor/dynorphin-dependent Axon Extementioning

confidence: 99%

“…We then exploited a previously generated Grb7 dominant negative mutant that could not be phosphorylated (14) to confirm the functionality of Grb7 in mediating the stimulating effect of EGF on axon extension. We compared the effects of WT Grb7 (WT CFP-Grb7) and this dominant negative mutant Grb7 (DM CFP-Grb7) in rat DRG neuron axon outgrowth experiments (Fig.…”

Section: Signal Of Egf To Stimulate Kor/dynorphin-dependent Axon Extementioning

confidence: 99%

“…5A, the full-length (containing KOR 5′-and 3′-UTRs) and 5′-UTR KOR reporters, but not the 3′-UTR reporter, showed increased activities after EGF treatment, suggesting the 5′-UTR of KOR mRNA as the target of EGF action. One crucial regulator for this 5′-UTR is its specific binding protein, Grb7 (14). We then examined the activity of Grb7 in mediating the effect of EGF by silencing the endogenous Grb7.…”

Section: Signal Of Egf To Stimulate Kor/dynorphin-dependent Axon Extementioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Tsai

Tsui

Pintar

et al. 2010

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

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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

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Section: Signal Of Egf To Stimulate Kor/dynorphin-dependent Axon Extecontrasting

confidence: 41%

Section: Signal Of Egf To Stimulate Kor/dynorphin-dependent Axon Extementioning

confidence: 99%

Section: Signal Of Egf To Stimulate Kor/dynorphin-dependent Axon Extementioning

confidence: 99%

Section: Signal Of Egf To Stimulate Kor/dynorphin-dependent Axon Extementioning

confidence: 99%

mentioning

confidence: 99%

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

Tsai

Tsui

Pintar

et al. 2010

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

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Intracellular RNA Localization and Localized Translation

Besse

2013

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Molecular determinants of the axonal mRNA transcriptome

Gomes

Merianda

Lee

et al. 2013

Developmental Neurobiology

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Axonal protein synthesis has been shown to play a role in developmental and regenerative growth, as well as in cell body responses to axotomy. Recent studies have begun to identify the protein products that contribute to these autonomous responses of axons. In the peripheral nervous system, intra-axonal protein synthesis has been implicated in the localized in vivo responses to neuropathic stimuli, and there is emerging evidence for protein synthesis in CNS axons in vivo. Despite that hundreds of mRNAs have now been shown to localize into the axonal compartment, knowledge of what RNA binding proteins are responsible for this is quite limited. Here, we review the current state of knowledge of RNA transport mechanisms, and highlight recently uncovered mechanisms for dynamically altering the axonal transcriptome. Both changes in the levels or activities of components of the RNA transport apparatus and alterations in transcription of transported mRNAs can effectively shift the axonal mRNA population. Consistent with this, the axonal RNA population shifts with development, with changes in growth state, and in response to extracellular stimulation. Each of these events must impact the transcriptional and transport apparatuses of the neuron, thus directly and indirectly modifying the axonal transcriptome.

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The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation

Cited by 51 publications

References 33 publications

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

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

Intracellular RNA Localization and Localized Translation

Molecular determinants of the axonal mRNA transcriptome

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