PT - JOURNAL ARTICLE AU - Max Koppers AU - Roberta Cagnetta AU - Toshiaki Shigeoka AU - Lucia C.S. Wunderlich AU - Sixian Zhao AU - Michael S. Minett AU - Anaïs Bellon AU - Clemens F. Kaminski AU - John. G. Flanagan AU - Christine E. Holt TI - Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons AID - 10.1101/673798 DP - 2019 Jan 01 TA - bioRxiv PG - 673798 4099 - http://biorxiv.org/content/early/2019/06/17/673798.short 4100 - http://biorxiv.org/content/early/2019/06/17/673798.full AB - During 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.