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Title: Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons
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. 
Keywords: UPS; axonal maturation; co-cultures; neuromuscular junction; presynaptic differentiation; proteasome; ribosomal proteins; ribosome; synapse formation; synaptogenesis
Issue Date: 23-Jul-2019
Publisher: Elsevier
Project: 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.). 
Serial title, monograph or event: Cell Reports
Volume: 28
Issue: 4
Abstract: 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.
ISSN: 22111247
DOI: 10.1016/j.celrep.2019.06.080
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais

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