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Título: | Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons | Autor: | 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. |
Palavras-chave: | UPS; axonal maturation; co-cultures; neuromuscular junction; presynaptic differentiation; proteasome; ribosomal proteins; ribosome; synapse formation; synaptogenesis | Data: | 23-Jul-2019 | Editora: | Elsevier | Projeto: | This work was funded by FEDER - Fundo Europeu de Desenvolvimento Regional, through COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT - Fundac¸ ~ao para a Ci^encia e a Tecnologia, under the projects PTDC/SAUNEU/ 104100/2008, EXPL/NEU-NMC/0541/2012, UID/BIM/04501/2013, UID/ NEU/04539/2019, POCI-01-0145-FEDER-007628, and CENTRO-01-0145- FEDER-000008:BrainHealth 2020, individual grants SFRH/BPD/84593/2012 (R.O.C.), PD/BD/114170/2016 (L.F.M.), SFRH/BPD/115546/2016 (M.M.), SFRH/BD/77789/2011 (J.R.P.), and SFRH/BD/139368/2018 (D.T.), and by Marie Curie Actions - IRG - 7th Research Framework Programme, and NIH grants R35NS111631 and NS056306 (S.R.J.). | Título da revista, periódico, livro ou evento: | Cell Reports | Volume: | 28 | Número: | 4 | Resumo: | 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. | URI: | https://hdl.handle.net/10316/106851 | ISSN: | 22111247 | DOI: | 10.1016/j.celrep.2019.06.080 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais |
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Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons.pdf | 4.45 MB | Adobe PDF | Ver/Abrir |
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