Oligodendrocyte differentiation and signaling after transferrin internalization: A mechanism of action

Autor: Natalia Cristina Fernandez, Maria Julia Perez, Juana M. Pasquini
Rok vydání: 2013
Předmět:
Male
MAP Kinase Signaling System
Transferrin receptor
Signalling
Biology
Proto-Oncogene Proteins c-fyn
environment and public health
Fyn tyrosine kinase
Ciencias Biológicas
Phosphatidylinositol 3-Kinases
FYN
Biología Celular
Microbiología
Developmental Neuroscience
Receptors
Transferrin
medicine
Animals
Phosphorylation
Rats
Wistar
Protein kinase B
Cells
Cultured
PI3K/AKT/mTOR pathway
Transferrin
Oligodendrocyte differentiation
Cell Differentiation
MEK/ERK pathways
Oligodendrocyte
Clathrin
Rats
Myelin basic protein
Receptor-internalization
Oligodendrocyte differentiation and transferrin
Oligodendroglia
medicine.anatomical_structure
Neurology
PI3K/Akt pathway
Cancer research
biology.protein
Female
Signal transduction
Proto-Oncogene Proteins c-akt
CIENCIAS NATURALES Y EXACTAS
Signal Transduction
Zdroj: Experimental Neurology. 248:262-274
ISSN: 0014-4886
DOI: 10.1016/j.expneurol.2013.06.014
Popis: 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. Fil: Perez, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina; Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Quimica Biologica. Cátedra de Química Biológica Patológica; Argentina; Fil: Fernandez, Natalia Cristina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina; Fil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
Databáze: OpenAIRE
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