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

• DOI: 10.17863/cam.46640
• Publication Date: 2019-11-20
• Authors: Koppers, Max; Cagnetta, Roberta; Shigeoka, Toshiaki; Wunderlich, Lucia CS; Vallejo-Ramirez, ...; Qiaojin Lin, Julie; Zhao, Sixian; Jakobs, Maximilia...; Dwivedy, Asha; Minett, Michael S; Bellon, Anaïs; Kaminski, Clemens F; Harris, William A; Flanagan, John G; Holt, Christine E
• Keywords: 0301 basic medicine; Retinal Ganglion Cells; Proteome; QH301-705.5; Science; Xenopus; RNA-binding protein; mRNA; Receptors, Cell Surface; Axon; guidance receptor; neuroscience; developmental biology; Xenopus laevis; 03 medical and health sciences; Animals; Retinal ganglion cell; human; local protein synthesis; RNA, Messenger; Biology (General); retinal ganglion cell; axon; 0303 health sciences; Q; R; RNA-Binding Proteins; xenopus; Axons; Guidance Receptor; Protein Biosynthesis; Medicine; Ribosomes; Research Article; Developmental Biology; Human; Neuroscience; Local Protein Synthesis; Signal Transduction

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.