Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons

Abstract
Data availability
Article and author information
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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).

The following data sets were generated

1. Koppers M
2. Cagnetta R
3. Shigeoka T
4. Wunderlich LCS
5. Vallejo-Ramirez P
6. Qiaojin Lin J
7. Zhao S
8. Jakobs M
9. Dwivedy A
10. Minett MS
11. Bellon A
12. Kaminski CF
13. Harris WA
14. Flanagan JG
15. Holt CE
(2019) Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons
NCBI Gene Expression Omnibus, GSE135338.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE135338
1. Koppers M
2. Cagnetta R
3. Shigeoka T
4. Wunderlich LCS
5. Vallejo-Ramirez P
6. Qiaojin Lin J
7. Zhao S
8. Jakobs M
9. Dwivedy A
10. Minett MS
11. Bellon A
12. Kaminski CF
13. Harris WA
14. Flanagan JG
15. Holt CE
(2019) LC-MSMS of DCC and Neuropilin-1 immunoprecipitated samples from Xenopus Laevis brains
PRIDE, PXD015650.

http://www.ebi.ac.uk/pride

The following previously published data sets were used

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Article and author information

Author details

Max Koppers

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Roberta Cagnetta

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Toshiaki Shigeoka

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Lucia CS Wunderlich

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7200-1713
Pedro Vallejo-Ramirez

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Julie Qiaojin Lin

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Sixian Zhao

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Maximilian AH Jakobs

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0879-7937
Asha Dwivedy

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Michael S Minett

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Anaïs Bellon

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Clemens F Kaminski

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5194-0962
William A Harris

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9995-8096
John Flanagan

Department of Cell Biology, Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Christine E Holt

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

For correspondence
ceh33@cam.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2829-121X

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

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.