CONICET | Buscador de Institutos y Recursos Humanos

Post-translational arginylation of proteins is mediated by Arginyltransferase (Ate1), which modifies multiple substrates, such components of actin cytoskeleton, and modulates biological processes during embryogenesis, cell migration, proliferation and neuronal growth; however, its role in glia cells is poorly understood. Oligodendrocytes (OLs) are responsible of myelin formation in the central nervous system (CNS), essential for the rapid propagation ofneuronal action potential as well as for metabolic support of axons.OLs are generated from OL precursor cells (OPC) that undergo morphological changes through differentiation and myelination. The aim of this study was to analyze the relevance of Ate1 in OLs during CNS myelination. Conditional deletion (cKO) of Ate1 from OLs with the Cnp-cre promoter resulted in differential changes on OL differentiation throughout CNS development. Ate1 cKO animals had reduced OLs (Sox10 + ) number in the corpus callosum (CC) atP14. But at P21, OLs number was unchanged and its maturation, defined by CC1 expression, appeared normal in the CC. However, in the spinal cord of cKO, the number of mature (CC1 + ) OLs was reduced, showing that deletion of Ate1 in OLs resulted in developmental delay that varies between different regions of the CNS. Additionally, local OPC proliferation was increased in the CC at P21 in Ate1 cKO mice, relative to control mice, whereas at the same time the astrocytes population was increased. These resultssuggest that deletion of Ate1 in OLs caused a localized increase ofOPC proliferation and a concomitant astrogliosis response. Future studies would address which proteins are modified by Ate1 during OLs maturation. Studies supported by FONCyT 2015.

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