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

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Cagnetta, Roberta 
Shigeoka, Toshiaki 
Wunderlich, Lucia CS  ORCID logo
Vallejo-Ramirez, Pedro  ORCID logo


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.



Research Article, Developmental Biology, Neuroscience, local protein synthesis, axon, guidance receptor, retinal ganglion cell, mRNA, RNA-binding protein, Human, Xenopus

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Netherlands Organisation for Scientific Research (Rubicon 019.161LW.033)
EPSRC (EP/L015889/1)
EPSRC (EP/H018301/1)
Wellcome Trust (3-3249/Z/16/Z)
Wellcome Trust (089703/Z/09/Z)
Wellcome Trust (085314/Z/08/Z)
Wellcome Trust (203249/Z/16/Z)
European Research Council (Advanced Grant 322817)