Rol de la arginilación postraducción de proteínas durante la autofagia en células de Schwann

FLORES MARTIN J; PALANDRI A; BONNET LV; HALLAK ME; GALIANO MR

Córdoba

Jornada; VIII Jornadas de Posgrado. II Jornadas de Ciencia y Tecnología; 2018

Fac. Cs. Químicas.UNC. Escuela de Posgrado

The role of the arginyl-protein transferase (Ate1) mediating the post-translational arginylation of proteins has been mainly studied in fibroblasts and muscle cells, however its function among nervous system components is poorly understood. Previous reports described that post-translational arginylation of proteins increased after injury of sciatic nerves whereas Ate1 activity did not change after optic nerve lesion. Our studies are aimed to determine whether such difference is related with whole nerve tissue or corresponds to a particular cell type. 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 of Schwann and decays later on. This variation of Ate1 expression parallels the recently described activation of autophagy in these cells. Moreover, a similar increase was found for arginylated calreticulin (R-CRT), an Ate1 modified protein, which also showed partial colocalization with markers of autophagy by confocal microscopy. Further analysis of sciatic nerve segments that were cultured under different conditions showed that the inhibition of proteasome with MG132 increased Ate1 levels, whereas autophagy inhibition with 3MA did not. As well the progress of myelin degradation gets more retarded by MG132 than by 3MA. To confirm if increased post-translational protein arginylation in Schwann cells corresponds to enhanced protein degradation by autophagy after peripheral nerve injury, new studies are currently performed with Ate1 conditional mutants. Moreover, our model will help to determine how Ate1 activity modulates the crosstalk between macroautophagy and ubiquitin-proteasome pathway of proteins degradation.