IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
artículos
Título:
Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action.
Autor/es:
PEREZ MJ; FERNANDEZ N; PASQUINI JM
Revista:
EXPERIMENTAL NEUROLOGY
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Lugar: Amsterdam; Año: 2013 vol. 248 p. 262 - 274
ISSN:
0014-4886
Resumen:
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 increasesmyelin basic protein, F3-contactin and â-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.
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.
â-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.