Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons

• Published in: Cell reports (Cambridge) Vol. 28; no. 4; pp. 864 - 876.e6
• Main Authors: Costa, Rui O., Martins, Helena, Martins, Luís F., Cwetsch, Andrzej W., Mele, Miranda, Pedro, Joana R., Tomé, Diogo, Jeon, Noo Li, Cancedda, Laura, Jaffrey, Samie R., Almeida, Ramiro D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-07-2019
• Subjects: axonal maturation; co-cultures; neuromuscular junction; presynaptic differentiation; proteasome; ribosomal proteins; ribosome; synapse formation; synaptogenesis; UPS; ribosomal proteins; proteasome; axonal maturation; neuromuscular junction; co-cultures; presynaptic differentiation; ribosome; UPS; synaptogenesis; synapse formation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.06.080

Ribosomes and a subset of cellular mRNAs are trafficked into axons of developing neurons. The axonal localization of translational machinery allows new proteins to be rapidly and locally synthesized during axonal growth and pathfinding. However, in mature neurons, axonal ribosomes are significantly reduced or even absent. The mechanism that elicits this removal is currently unknown. Here, we demonstrate that synapse formation is the trigger for ribosome reduction in mature axons. In vivo analysis shows that axonal ribosome levels decrease in rat brain at a developmental stage coincident with synapse formation. Next, we observe in vitro that different synaptogenic inducers trigger an overall decrease of ribosomal proteins and rRNA in the axons of spinal motor neurons. We further observe that this process is dependent on the ubiquitin-proteasome system but not on autophagy. Together, these data identify synaptogenesis as the long missing biological trigger that leads to ribosome disappearance during axonal maturation.
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•Synapse formation induces intra-axonal ribosomal decrease•Ribosomes are degraded by ubiquitin proteasome system upon axonal maturation
The mechanism behind the striking loss of ribosomes from axons during neuronal maturation is unknown. Using in vivo and in vitro models, including neuron-muscle co-cultures and combining biochemistry and imaging techniques, Costa et al. demonstrate that synapse formation triggers ribosome reduction by a mechanism involving the ubiquitin-proteasome system.