Studying the role of post-translational protein arginylation during autophagy elicited in Schwann cells after nerve injury.

JESICA FLORES-MARTIN; LAURA V. BONNET; MAURICIO R. GALIANO; MARTA E. HALLAK

Buenos Aires

Congreso; Buenos Aires Reasearch Conferences on Autophagy; 2017

Facultad de Farmacia y Bioquimica - UBA

In nervous system, the enzyme arginyl-protein transferase (Ate1), responsible of post-translationalarginylation of proteins, was postulated to modify proteins that are targeted to proteasomaldegradation. Previous reports described that Ate1 activity gets increased after injury of sciaticnerves. In a similar injury model was reported that autophagy is activated in myelinating Schwanncells. In this study we performed primary Schwann cell cultures from P8 rats to model peripheralnerve injury. By Western blot, we found that Ate1 expression reaches a maximum in DIV 5 culturesand 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 modifiedprotein, which also showed partial colocalization with markers of autophagy. Further analysis ofsciatic nerve segments that were cultured under different conditions showed that the proteasomeinhibitor MG132 increased Ate1 levels, whereas the autophagy inhibitor 3MA did not. As well theprogress of myelin degradation gets more retarded by MG132 than by 3MA.These results suggestthat Ate1 activity modulates the crosstalk between macroautophagy and ubiquitin-proteasomepathway of proteins degradation. Respect this hyp