Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons

• Autor(a) principal: Costa, Rui O.
• Data de Publicação: 2019
• Outros Autores: 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.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/106851; https://doi.org/10.1016/j.celrep.2019.06.080
• topic: UPS; axonal maturation; co-cultures; neuromuscular junction; presynaptic differentiation; proteasome; ribosomal proteins; ribosome; synapse formation; synaptogenesis; Animals; Axons; Cell Differentiation; Female; HEK293 Cells; Humans; Mice; Neuromuscular Junction; Presynaptic Terminals; Proteasome Endopeptidase Complex; RNA, Ribosomal; Rats, Sprague-Dawley; Ribosomes; Synapses; Ubiquitin; Neurogenesis

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.