Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons
Extrinsic cues trigger the local translation of specific mRNAs in growing axons via cell surface receptors. The coupling of ribosomes to receptors has been proposed as a mechanism linking signals to local translation but it is not known how broadly this mechanism operates, nor whether it can selecti...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/48718 |
| _version_ | 1811181469737943040 |
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| author | Max Koppers Roberta Cagnetta Toshiaki Shigeoka Lucia CS Wunderlich Pedro Vallejo-Ramirez Julie Qiaojin Lin Sixian Zhao Maximilian AH Jakobs Asha Dwivedy Michael S Minett Anaïs Bellon Clemens F Kaminski William A Harris John G Flanagan Christine E Holt |
| author_facet | Max Koppers Roberta Cagnetta Toshiaki Shigeoka Lucia CS Wunderlich Pedro Vallejo-Ramirez Julie Qiaojin Lin Sixian Zhao Maximilian AH Jakobs Asha Dwivedy Michael S Minett Anaïs Bellon Clemens F Kaminski William A Harris John G Flanagan Christine E Holt |
| author_sort | Max Koppers |
| collection | DOAJ |
| description | Extrinsic cues trigger the local translation of specific mRNAs in growing axons via cell surface receptors. The coupling of ribosomes to receptors has been proposed as a mechanism linking signals to local translation but it is not known how broadly this mechanism operates, nor whether it can selectively regulate mRNA translation. We report that receptor-ribosome coupling is employed by multiple guidance cue receptors and this interaction is mRNA-dependent. We find that different receptors associate with distinct sets of mRNAs and RNA-binding proteins. Cue stimulation of growing Xenopus retinal ganglion cell axons induces rapid dissociation of ribosomes from receptors and the selective translation of receptor-specific mRNAs. Further, we show that receptor-ribosome dissociation and cue-induced selective translation are inhibited by co-exposure to translation-repressive cues, suggesting a novel mode of signal integration. Our findings reveal receptor-specific interactomes and suggest a generalizable model for cue-selective control of the local proteome. |
| first_indexed | 2024-04-11T09:18:16Z |
| format | Article |
| id | doaj.art-9b3b40d5ede643c89c36904b516f8db7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:18:16Z |
| publishDate | 2019-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9b3b40d5ede643c89c36904b516f8db72022-12-22T04:32:17ZengeLife Sciences Publications LtdeLife2050-084X2019-11-01810.7554/eLife.48718Receptor-specific interactome as a hub for rapid cue-induced selective translation in axonsMax Koppers0https://orcid.org/0000-0002-7751-1082Roberta Cagnetta1Toshiaki Shigeoka2Lucia CS Wunderlich3https://orcid.org/0000-0001-7200-1713Pedro Vallejo-Ramirez4https://orcid.org/0000-0002-7879-6761Julie Qiaojin Lin5https://orcid.org/0000-0002-2669-6478Sixian Zhao6Maximilian AH Jakobs7https://orcid.org/0000-0002-0879-7937Asha Dwivedy8Michael S Minett9Anaïs Bellon10Clemens F Kaminski11https://orcid.org/0000-0002-5194-0962William A Harris12https://orcid.org/0000-0002-9995-8096John G Flanagan13Christine E Holt14https://orcid.org/0000-0003-2829-121XDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United KingdomDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Cell Biology, Harvard Medical School, Boston, United StatesDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomExtrinsic cues trigger the local translation of specific mRNAs in growing axons via cell surface receptors. The coupling of ribosomes to receptors has been proposed as a mechanism linking signals to local translation but it is not known how broadly this mechanism operates, nor whether it can selectively regulate mRNA translation. We report that receptor-ribosome coupling is employed by multiple guidance cue receptors and this interaction is mRNA-dependent. We find that different receptors associate with distinct sets of mRNAs and RNA-binding proteins. Cue stimulation of growing Xenopus retinal ganglion cell axons induces rapid dissociation of ribosomes from receptors and the selective translation of receptor-specific mRNAs. Further, we show that receptor-ribosome dissociation and cue-induced selective translation are inhibited by co-exposure to translation-repressive cues, suggesting a novel mode of signal integration. Our findings reveal receptor-specific interactomes and suggest a generalizable model for cue-selective control of the local proteome.https://elifesciences.org/articles/48718local protein synthesisaxonguidance receptorretinal ganglion cellmRNARNA-binding protein |
| spellingShingle | Max Koppers Roberta Cagnetta Toshiaki Shigeoka Lucia CS Wunderlich Pedro Vallejo-Ramirez Julie Qiaojin Lin Sixian Zhao Maximilian AH Jakobs Asha Dwivedy Michael S Minett Anaïs Bellon Clemens F Kaminski William A Harris John G Flanagan Christine E Holt Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons eLife local protein synthesis axon guidance receptor retinal ganglion cell mRNA RNA-binding protein |
| title | Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons |
| title_full | Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons |
| title_fullStr | Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons |
| title_full_unstemmed | Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons |
| title_short | Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons |
| title_sort | receptor specific interactome as a hub for rapid cue induced selective translation in axons |
| topic | local protein synthesis axon guidance receptor retinal ganglion cell mRNA RNA-binding protein |
| url | https://elifesciences.org/articles/48718 |
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