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Elife. 2019 Nov 20;8. pii: e48718. doi: 10.7554/eLife.48718.

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

Author information

1
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
2
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
3
Department of Cell Biology, Harvard Medical School, Boston, United States.
#
Contributed equally

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.

KEYWORDS:

RNA-binding protein; axon; developmental biology; guidance receptor; human; local protein synthesis; mRNA; neuroscience; retinal ganglion cell; xenopus

PMID:
31746735
DOI:
10.7554/eLife.48718
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