PAD2-Mediated Citrullination Contributes to Efficient Oligodendrocyte Differentiation and Myelination

Falcão, Ana Mendanha; Meijer, Mandy; Scaglione, Antonella; Rinwa, Puneet; Agirre, Eneritz; Liang, Jialiang; Larsen, Sara C.; Heskol, Abeer; Frawley, Rebecca; Klingener, Michael; Varas-Godoy, Manuel; Raposo, Alexandre A.S.F.; Ernfors, Patrik; Castro, Diogo S.; Nielsen, Michael L.; et. al.

Abstract

Citrullination, the deimination of peptidylarginine residues into peptidylcitrulline, has been implicated in the etiology of several diseases. In multiple sclerosis, citrullination is thought to be a major driver of pathology through hypercitrullination and destabilization of myelin. As such, inhibition of citrullination has been suggested as a therapeutic strategy for MS. Here, in contrast, we show that citrullination by peptidylarginine deiminase 2 (PAD2) contributes to normal oligodendrocyte differentiation, myelination, and motor function. We identify several targets for PAD2, including myelin and chromatin-related proteins, implicating PAD2 in epigenomic regulation. Accordingly, we observe that PAD2 inhibition and its knockdown affect chromatin accessibility and prevent the upregulation of oligodendrocyte differentiation genes. Moreover, mice lacking PAD2 display motor dysfunction and a decreased number of myelinated axons in the corpus callosum. We conclude that citrullination contributes to proper oligodendrocyte lineage progression and myelination.

Más información

Título según WOS: PAD2-Mediated Citrullination Contributes to Efficient Oligodendrocyte Differentiation and Myelination
Título según SCOPUS: PAD2-Mediated Citrullination Contributes to Efficient Oligodendrocyte Differentiation and Myelination
Título de la Revista: CELL REPORTS
Volumen: 27
Número: 4
Editorial: Cell Press
Fecha de publicación: 2019
Página de inicio: 1090
Página final: +
Idioma: English
DOI:

10.1016/j.celrep.2019.03.108

Notas: ISI, SCOPUS