Cellular and Molecular Neurobiology
Author: Mauricio Raul Galiano | email: mauricio.galiano@unc.edu.ar
Anabela Palandri 1°, Laura Vanesa Bonnet 1°, Maria Gimena Farias 1°, Marta Elena Hallak 1°, Mauricio Raul Galiano 1°
1° Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), Dpto. Química Biológica Ranwel Caputto, Fac. Ciencias Químicas, Univ. Nacional de Cordoba
Arginyl-tRNA-protein transferase (Ate1) mediates the post-translational addition of arginine from Arg-tRNA to different protein substrates, participating in cellular processes such as cell migration, cytoskeletal arrangement, and apoptosis. In mammalian central nervous system (CNS), Ate1 was found to modulate neuronal differentiation and associated with neurodegenerative disorders. Our studies aim to elucidate the role of Ate1 in glial development, including oligodendrocyte (OL) differentiation and myelination in the CNS. In primary OL cultures, we found a peak in Ate1 protein expression during the myelination process. Whereas transcriptional downregulation of Ate1 reduces the number of OL processes and branching complexity. To study Ate1 function and axonal myelination in vivo, we conditionally ablated Ate1 in mice from OLs using CNP-promoter (Ate1-KO mice). In the corpus callosum of 14-day-old Ate1-KO mice, we found a temporary delay in OL differentiation, compared to wild-type controls, while local proliferation of OL precursor cells normalizes mature OL populations in 21-day-old Ate1-KO mice. However, 5-month-old Ate1-KO mice showed reductions in mature OLs and myelin thickness along with subtle alterations in motor behaviors. Our results indicate that Ate1 contributes to proper OL differentiation and axonal myelination, in part by modulating the OL actin cytoskeleton. These findings reveal an essential role for protein arginylation in the maintenance of CNS myelin.