Role of post-translational arginylation proteins in glial cells during CNS myelination

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

Montreal

Congreso; ISN-ASN Meeting; 2019

International society for neurochemistry

Within the central nervous system (CNS), a majority of axons are ensheathed with lipid-rich myelin produced by myelinating oligodendrocytes (OLs). Myelin sheaths allow axons to conduct more rapid propagation of electrical impulses to facilitate sensory, motor and cognitive function. OLs are generated from OL precursor cells (OPC) undergoing a number of developmental stages followed by terminal differentiation and myelination. Protein arginylation is a post-translational modification mediated by the Arginyl-tRNA transferase (Ate1), which is an essential mouse gene, whose deletion causes embryonic lethality and severe cardiovascular defects. Ate1 regulates many fundamental biological processes, and targets a large number of proteins in vivo, including cytoskeletal proteins that play direct roles in cell migration; however, the underlying molecular mechanisms are still poorly understood, especially in CNS. The aim of this study was to analyze the impact of Ate1 enzyme in developing OLs during CNS myelination. The conditional deletion (cKO) of Ate1 from OLs with the Cnp-cre promoter resulted in differential impact on OL differentiation throughout CNS development. Ate1 cKO animals had reduced OL number in the corpus callosum (CC) at postnatal day 14 (P14), suggesting a deficit in OL production and maturation. At P21, OLs number was unchanged and its maturation as defined by CC1 expression appeared normal in the CC; however, in the spinal cord CC1+ mature 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. These results suggest that enhanced OPC proliferation is an early response to the altered OL signaling initiated by the deletion of Ate1 in glial cells during CNS myelination.