Open AccessOligodendrocyte differentiation and signaling after transferrin internalization: A mechanism of action
Author(s) -
Miguel A. Pérez,
Natalia Cristina Fernández,
Juana M. Pasquini
Publication year - 2013
Publication title -
experimental neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.779
H-Index - 186
eISSN - 1090-2430
pISSN - 0014-4886
DOI - 10.1016/j.expneurol.2013.06.014
Subject(s) - fyn , microbiology and biotechnology , biology , oligodendrocyte , mapk/erk pathway , proto oncogene tyrosine protein kinase src , endocytosis , protein kinase b , signal transduction , myelin , chemistry , biochemistry , neuroscience , receptor , central nervous system
Oligodendrocytes are the cells producing the myelin membrane around the axons in the central nervous system and, although apotransferrin (aTf) is required for oligodendrocyte differentiation, the underlying mechanisms are not fully understood. Fyn tyrosine kinase, a member of the Src family of proteins, has been shown to play an important role in myelination by up-regulating the expression of myelin basic protein; however, a molecular link between aTf and Fyn kinase signaling pathway during oligodendrocytes differentiation has not been established yet. Our aim was to investigate whether Fyn kinase, MEK/ERK and PI3K/Akt signaling pathways are required for aTf-stimulation of oligodendrocyte differentiation and also to determine if the transferrin receptor is involved in these mechanisms. Treatment of primary cultures of oligodendroglial precursor cells with aTf leads to Fyn kinase activation by a mechanism that involves transferrin receptor. In turn, Fyn kinase activation promotes MEK-mediated transient phosphorylation of ERK1/2. On the other hand, transferrin receptor internalization also produces rapid and sustained activation of Akt, which involves phosphatidylinositol 3-kinase (PI3K) activation. Finally, aTf incorporated through clathrin-mediated endocytosis increases myelin basic protein, F3-contactin and β-tubulin through Fyn/MEK/ERK pathways, as well as an activation of the PI3K/Akt pathway. Our results also demonstrate that the activation of the pathways necessary for oligodendroglial precursor cell maturation is dependent on AP2 recruitment onto the plasma membrane for clathrin-mediated endocytosis of transferrin receptor.