UC Research discovers how the puzzle pieces of the nervous system fit
A research team of the Center for Neuroscience and Cell Biology of the University of Coimbra (CNC-UC) has uncovered an important regulatory mechanism in the development of the nervous system.


The discovery of how the pieces of this complex puzzle fit – aim of the study entitled “Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons”, recently published in the high-considered Cell Reports – may open new paths in the study of spinal injuries such as in Amyotrophic Lateral Sclerosis.

The research – conducted by CNC-UC, in partnership with the Cornell University (USA), Italian Institute of Technology (Italy) and the National University of  Seoul (South Korea) – allowed to understand how the synaptogenesis process leads to the disappearance of the ribosomes during axon maturation. To understand the complex scientific concepts in each of these pieces – synaptogenesis, ribosome or axon – it matters, beforehand, to understand how the puzzle works. Our neurons are divided in 3 structures: cell body or soma,  dendrites and axons. The last one works as a communication channel for neurons, allowing the contact with other neurons or cells in our body, by a specialized structure known as synapse, which allows the information transmission between nervous cells. During development of the nervous system, neurons undergo a maturation process, in which significative transformations occur by the axon level: one of these modifications is the change in the number of ribosomes – little structures that work as protein production machines.

Well, in the study published in Cell Reports, the research team coordinated by CNC-UC reveals why axons lose part of their ribosomes after maturation. “This work aimed to identify the mechanisms that regulate this alteration, since, in a not understood manner, after axon maturation, the number of ribosomes in axons is reduced”, explains the leader of the research team, Ramiro Almeida (also Professor at the University of Aveiro).

The study used animal and cell models, and in both cases, it was observed that the reduction of ribosomes was due to the formation of new synapses. The research team believes that this reduction occurs after neuron maturation, due to the less need for protein formation. And it uncovered that this reduction is mediated by the ubiquitin-proteasome system (responsible for the degradation of cell components). “As it was referred, after the formation of synapses we observed that the number of ribosomes decreased. By researching why, we found that the ubiquitin-proteasome system was the responsible for eliminating and reducing the number of ribosomes in axons. A process also induced by the formation of synapses”, refers Rui Costa, also researcher at CNC-UC and 1st author of the study.

This conclusions might have an impact relevant in the study of spinal injuries, as referred by both researchers. “The study of other research groups demonstrated that in a neuronal injury situation, among other processes, the number of ribosomes in axons increases, and these behave in a similar way to immature neurons. Our study shows which mechanism in the regulation of ribosome level and their importance in the development of the nervous system. In the future, the understanding of these processes – or other puzzle pieces – might help relief the damage caused by these injuries, as well as in diseases such as Amyotrophic Lateral Sclerosis”, conclude.

Other than Rui Costa and Ramiro Almeida, the sutyd “Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons”, had the participation of the CNC researchers Helena Martins, Luís Martins, Miranda Mele, Joana Pedro and Diogo Tomé, and was financed by FEDER, COMPETE2020, FCT, Marie Curie Actions and NIH.

Credits: João Cardoso, Ramiro Almeida, Rui Costa, Rui Simões
Foto: João Cardoso
Financiado por Fundos FEDER através do Programa Operacional Factores de Competitividade – COMPETE 2020 e por Fundos Nacionais através da FCT – Fundação para a Ciência e a Tecnologia no âmbito do projecto Estratégico com referência atribuida pelo COMPETE: POCI-01-0145-FEDER-007440

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