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Fyn kinase is involved in oligodendroglial cell differentiation induced by apotransferrin

Authors

  • M.J. Perez,

    1. Department of Biological Chemistry, Institute of Biological and Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina
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    • The first two authors contributed equally to this work.

  • E.H. Ortiz,

    1. Department of Biological Chemistry, Institute of Biological and Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina
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    • The first two authors contributed equally to this work.

  • M. Roffé,

    1. Department of Biological Chemistry, Institute of Biological and Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina
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  • E.F. Soto,

    1. Department of Biological Chemistry, Institute of Biological and Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina
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  • J.M. Pasquini

    Corresponding author
    1. Department of Biological Chemistry, Institute of Biological and Physical Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires-CONICET, Buenos Aires, Argentina
    • Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Junín 956- C1113AAD, Buenos Aires, Argentina
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Abstract

Mechanisms that regulate oligodendroglial cell (OLGc) differentiation are the focus of intensive research in the field of cellular and molecular neurobiology. We have previously shown that the addition of apotransferrin (aTf) to primary OLGc cultures accelerates their differentiation and induces an increase in the expression of different components of the myelin cytoskeleton (CSK) such as actin, tubulin, and some of the microtubule-associated proteins, particularly the stable tubulin only peptide (STOP). Fyn protein-tyrosine kinase (Fyn kinase), a member of the Src family, participates in signalling pathways that regulate OLGs/myelin cytoskeletal reorganization. It is essential for myelin development in the central nervous system (CNS), and its absence results in hypomyelination. In the present study, we used both primary cell and N19 cell line cultures to investigate further the mechanisms of action involved in the accelerated differentiation of OLGcs induced by aTf. In particular, we were interested in studying the participation of Fyn kinase in the different pathways involved in the reorganization of the OLGc/myelin cytoskeleton. In agreement with results already published, we found that in OLGcs, Fyn kinase is associated with Tau and tubulin. Using a dominant-negative of Tau in which the Fyn-Tau-microtubules (MTs) interaction is blocked, we found that aTf was unable to induce OLGc morphological differentiation. It was also observed that aTf decreases the activated RhoA content in coincidence with a redistribution of actin immunoreactivity. These results give support to our hypothesis that Fyn kinase plays a key role in the differentiation process of OLGcs promoted by aTf. © 2008 Wiley-Liss, Inc.

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