Ribosome-Associated Vesicles promote activity-dependent local translation

• Published in: bioRxiv
• Main Authors: Martin-Solana, Eva, Carter, Stephen D, Donahue, Eric K F, Ning, Jiying, Glausier, Jill R, Preisegger, Matias A, Eisenman, Leanna, Joseph, Paul N, Bouchet-Marquis, Cedric, Wu, Ken, Mobini, Catherina L, Frantz, Amber N, Puig, Stephanie, Hampton, Cheri M, Kabbani, Nadine, Jensen, Grant J, Watkins, Simon C, Deisseroth, Karl, Fenno, Lief E, Gold, Michael S, Wills, Zachary P, Burkewitz, Kristopher, Das, Sulagna, Freyberg, Zachary
• Format: Journal Article
• Language: English
• Published: 10.06.2024
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2024.06.07.598007

Local protein synthesis in axons and dendrites underpins synaptic plasticity. However, the composition of the protein synthesis machinery in distal neuronal processes and the mechanisms for its activity-driven deployment to local translation sites remain unclear. Here, we employed cryo-electron tomography, volume electron microscopy, and live-cell imaging to identify Ribosome-Associated Vesicles (RAVs) as a dynamic platform for moving ribosomes to distal processes. Stimulation via chemically-induced long-term potentiation causes RAV accumulation in distal sites to drive local translation. We also demonstrate activity-driven changes in RAV generation and dynamics in vivo, identifying tubular ER shaping proteins in RAV biogenesis. Together, our work identifies a mechanism for ribosomal delivery to distal sites in neurons to promote activity-dependent local translation.Local protein synthesis in axons and dendrites underpins synaptic plasticity. However, the composition of the protein synthesis machinery in distal neuronal processes and the mechanisms for its activity-driven deployment to local translation sites remain unclear. Here, we employed cryo-electron tomography, volume electron microscopy, and live-cell imaging to identify Ribosome-Associated Vesicles (RAVs) as a dynamic platform for moving ribosomes to distal processes. Stimulation via chemically-induced long-term potentiation causes RAV accumulation in distal sites to drive local translation. We also demonstrate activity-driven changes in RAV generation and dynamics in vivo, identifying tubular ER shaping proteins in RAV biogenesis. Together, our work identifies a mechanism for ribosomal delivery to distal sites in neurons to promote activity-dependent local translation.