CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Studying the role of post-translational protein arginylation during autophagy elicited in Schwann cells after nerve injury
Autor/es:
BONNET, LV; GALIANO MR; FLORES MARTIN J; HALLAK ME
Lugar:
Buenos Aires
Reunión:
Workshop; Buenos Aires Research Conferences on Autophagy. Molecular Mechanism in Biology and Diseases; 2017
Resumen:
In nervous system, the enzyme arginyl-protein transferase (Ate1), responsible of post-translational arginylation of proteins, was postulated to modify proteins that are targeted to proteasomal degradation. Previous reports described that Ate1 activity gets increased after injury of sciatic nerves. In a similar injury model was reported that autophagy is activated in myelinating Schwann cells. In this study we performed primary Schwann cell cultures from P8 rats to model peripheral nerve injury. By Western blot, we found that Ate1 expression reaches a maximum in DIV 5 cultures and decays later on; a profile that parallels the activation of autophagy shown by different markers. Moreover, a similar increase was found for arginylated calreticulin (R-CRT), an Ate1 modified protein, which also showed partial colocalization with markers of autophagy. Further analysis of sciatic nerve segments that were cultured under different conditions showed that the proteasome inhibitor MG132 increased Ate1 levels, whereas the autophagy inhibitor 3MA did not. As well the progress of myelin degradation gets more retarded by MG132 than by 3MA.These results suggest that Ate1 activity modulates the crosstalk between macroautophagy and ubiquitin-proteasome pathway of proteins degradation. Respect this hypothesis, new studies are currently performed with Ate1 conditional mutants to confirm our model.