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Receptor-specific Interactome As A Hub For Rapid Cue-induced Selective Translation In Axons

Max Koppers, Roberta Cagnetta, Toshiaki Shigeoka, Lucia C.S. Wunderlich, Sixian Zhao, Michael S. Minett, Anaïs Bellon, Clemens F. Kaminski, John. G. Flanagan, Christine E. Holt

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AbstractDuring neuronal wiring, extrinsic cues trigger the local translation of specific mRNAs in 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 bind to distinct sets of mRNAs and RNA-binding proteins. Cue stimulation induces rapid dissociation of ribosomes from receptors and the selective translation of receptor-specific mRNAs in retinal axon growth cones. Further, we show that receptor-ribosome dissociation and cue-induced selective translation are inhibited by simultaneous exposure to translation-repressive cues, suggesting a novel mode of signal integration. Our findings reveal receptor-specific interactomes and provide a general model for the rapid, localized and selective control of cue-induced translation.