• Home
  • Search Results
  • PAD2-Mediated Citrullination Contributes to Efficient Oligodendrocyte Differentiation and Myelination.

PAD2-Mediated Citrullination Contributes to Efficient Oligodendrocyte Differentiation and Myelination.

Cell reports (2019-04-25)
Ana Mendanha Falcão, Mandy Meijer, Antonella Scaglione, Puneet Rinwa, Eneritz Agirre, Jialiang Liang, Sara C Larsen, Abeer Heskol, Rebecca Frawley, Michael Klingener, Manuel Varas-Godoy, Alexandre A S F Raposo, Patrik Ernfors, Diogo S Castro, Michael L Nielsen, Patrizia Casaccia, Gonçalo Castelo-Branco
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Accutase® solution, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Tamoxifen, ≥99%
Sigma-Aldrich
Poly-L-lysine solution, 0.01%, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Doxycycline hyclate
Sigma-Aldrich
Fibronectin bovine plasma, solution, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Y-27632 dihydrochloride, ≥98% (HPLC)
Sigma-Aldrich
Donkey serum
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid
Sigma-Aldrich
DAPT, ≥98% (HPLC), solid
Sigma-Aldrich
3,3′,5-Triiodo-L-thyronine sodium salt, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Monoclonal Anti-Glial Fibrillary Acidic Protein (GFAP) antibody produced in mouse, clone G-A-5, ascites fluid
Sigma-Aldrich
Cytosine β-D-arabinofuranoside, crystalline, ≥90% (HPLC)
Sigma-Aldrich
Anti-Mouse IgG (whole molecule)–Peroxidase antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
2-Chloroacetamide, ≥98%
Sigma-Aldrich
N-Methyl-D-aspartic acid, ≥98% (TLC), solid
Sigma-Aldrich
Monoclonal Anti-GABA antibody produced in mouse, clone GB-69, ascites fluid
Sigma-Aldrich
Anti-Rabbit IgG (whole molecule), F(ab′)2 fragment−Peroxidase antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
ChIPAb+ Acetyl-Histone H3 (Lys27) - ChIP Validated Antibody and Primer Set, clone CMA309, from mouse