Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons
- University of Cambridge, United Kingdom
- Harvard Medical School, United States
Abstract
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.
Data availability
RNA-sequencing data associated with this manuscript has been deposited on the GEO database (identifier GSE135338).All proteomics data associated with this manuscript has been uploaded to the PRIDE online repository (identifier: PXD015650).
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Receptor-specific interactome as a hub for rapid cue-induced selective translation in axonsNCBI Gene Expression Omnibus, GSE135338.
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Unstressed HeLa cells and ELAVL1/HuR knock down conditions: polyA RNA-Seq, small RNA-Seq, and PAR-CLIPNCBI Gene Expression Omnibus, GSE29943.
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FMR1 targets distinct mRNA sequence elements to regulate protein expressionNCBI Gene Expression Omnibus, GSE39686.
Article and author information
Author details
Lucia CS Wunderlich
Maximilian AH Jakobs
Clemens F Kaminski
Funding
Netherlands Organization for Scientific Research (Rubicon 019.161LW.033)
- Max Koppers
Wellcome Trust (085314/Z/08/Z)
- Christine E Holt
Wellcome Trust (203249/Z/16/Z)
- Christine E Holt
European Research Council (Advanced Grant 322817)
- Christine E Holt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were approved by the University of Cambridge Ethical Review Committee in compliance with the University of Cambridge Animal Welfare Policy. This research has been regulated under the Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 following ethical review by the University of Cambridge Animal Welfare and Ethical Review Body (AWERB) and under project license PPL80/2198.
Copyright
© 2019, Koppers et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons
eLife 8:e48718.
https://doi.org/10.7554/eLife.48718
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