Deletion of the arginyltransferase gene in oligodendrocytes impairs myelination

PALANDRI ANABELA; BONNET, LAURA V.; JÉSICA FLORES MARTÍN; HALLAK, MARTA E.; GALIANO, MAURICIO R.

Carlos Paz, Córdoba

Congreso; XXXIV Reunión Anual SAN 2019; 2019

Sociedad Argentina de investigación en Neurociencias

Arginyltransferase (Ate1) adds an arginine residue to multiple protein substrates; whose post-translational modification modulate cellular processes such as migration, proliferation and neuronal growth; however, its role in Central Nervous System (CNS) is still uncertain. Oligodendrocyte precursor cells (OPCs) undergo morphological changes during differentiation into mature oligodendrocytes (OLs) in the CNS. The later generate the myelin that surrounds axons for rapid propagation of action potential. This study was aimed to elucidate the role of Ate1 through CNS myelination. Conditional deletion (cKO) of Ate1 from OLs with the Cnp-cre promoter resulted in differential changes on OL differentiation throughout CNS development. Analysis of OL populations in the corpus callosum (CC) shows that cKO mice at P14 have a reduced number of total (Sox10+) OLs respect control mice. Whereas at P21, Sox10 and mature OLs (CC1+) appear normal. Concomitantly at P21, increased proliferation of OPC and astrocytes populations was found in the CC of cKO mice. Nonetheless, a reduced number of CC1+ OLs was determined in the spinal cord of cKO, showing a delay in the maturation of OL between different CNS regions of Ate1 cKO mice. Hence, deletion of Ate1 in OLs induced an increase of local OPC proliferation together with astrogliosis response, which may compromise the myelin maintenance of adult mice. Future studies will address which proteins involved in OLs maturation are substrates of Ate1.