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Cell Rep. 2019 Jul 23;28(4):864-876.e6. doi: 10.1016/j.celrep.2019.06.080.

Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons.

Author information

1
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal. Electronic address: ruiocosta@gmail.com.
2
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
3
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal; PhD Programme in Experimental Biology and Biomedicine (PDBEB), Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
4
NBT - Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy.
5
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
6
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; iBiMED - Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
7
Institute of Advanced Machinery and Design, Seoul National University, Seoul, Republic of Korea; Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul, Republic of Korea.
8
NBT - Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa, Italy; Dulbecco Telethon Institute, Roma, Italy.
9
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10065, USA.
10
Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal; iBiMED - Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal. Electronic address: ramirodalmeida@gmail.com.

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.

KEYWORDS:

UPS; axonal maturation; co-cultures; neuromuscular junction; presynaptic differentiation; proteasome; ribosomal proteins; ribosome; synapse formation; synaptogenesis

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