Collapsin response mediator protein-2 phosphorylation promotes the reversible retraction of oligodendrocyte processes in response to non-lethal oxidative stress

FERNANDEZ GAMBA A; LEAL MC; MAAROUF CL; RICHTER-LANDSBERG C; WU T; MORELLI L; ROHER AE; CASTAÑO EM

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012 vol. 121 p. 185 - 195

0022-3042

The extension of processes of oligodendrocyte (OLG) andtheir precursor cells are crucial for migration, axonal contactand myelination. Here we show that a non-lethal oxidativestress induced by 3-nitropropionic acid (3-NP) elicited a rapidshortening of processes (24%) in primary OLGs and in oli-godendroglial cell line (OLN-93) cells (36%) as comparedwith vehicle-exposed cells. This was reversible and preventedby antioxidants. Proteomics of OLG lysates with and without3-NP treatment yielded collapsin response mediator protein 2(CRMP-2) as a candidate effector molecule. Inhibition of rhokinase was sufficient to prevent process retraction in bothOLGs and OLN-93 cells. Oxidative stress increased phos-phorylation of CRMP-2 at T555 that was completely preventedby Y27632. Moreover, transfection of OLN-93 cells with themutant CRMP-2 T555A which cannot be phosphorylated byrho kinase, prevented process shortening induced by 3-NP ascompared with wild-type CRMP-2. Our results suggest a rolefor endogenous reactive oxygen species in a pathway thatregulates OLG process extension. The vulnerability of latemyelinated neurons in the adult brain and the presence ofwhite matter pathology in human dementias warrant the studyof this oligodendroglial pathway in the early stages of neuro-degenerative conditions characterized by oxidative stress.Keywords: Alzheimer‘s disease, axonal myelination, CRMP-2, oligodendrocyte, oxidative stress, rho kinase