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The Journal of Neuroscience, February 1, 2002, 22(3):698-707
Process Outgrowth of Oligodendrocytes Is Promoted by Interaction
of Fyn Kinase with the Cytoskeletal Protein Tau
Corinna
Klein1,
Eva-Maria
Krämer1,
Anne-Marie
Cardine2,
Burkhardt
Schraven2,
Roland
Brandt1, and
Jacqueline
Trotter1
Departments of 1 Neurobiology and
2 Immunology, University of Heidelberg, 69120 Heidelberg,
Germany
Fyn kinase plays an important role during myelination and has been
shown to promote morphological differentiation of cultured oligodendrocytes. We analyzed the downstream targets of Fyn kinase in
oligodendrocytes. Because process outgrowth and wrapping of axons
involve cytoskeletal rearrangement, we focused on cytoskeletal proteins
linked to Fyn. Here we demonstrate that Fyn binds to the cytoskeletal
proteins Tau and -Tubulin in oligodendrocytes. Tau interacts with
the Fyn SH3 domain whereas -Tubulin binds to the Fyn SH2 and SH3
domains. To study the function of the Fyn-Tau interaction in
oligodendrocytes, we designed a Tau deletion mutant that would compete
with endogenous Tau-Fyn binding in transfected cells. The mutant Tau
protein binds to the Fyn SH3 domain but lacks the microtubuli
interaction domain and thus cannot bind to microtubuli. In the presence
of the mutant Tau protein, a reduction of the process number and
process length in oligodendroglial cells was observed. This effect is
likely to be caused by interference with the Fyn-Tau-microtubuli
cascade rather than inactivation of the kinase, because Fyn bound to
the mutant Tau retains activity. A similar inhibition of process
outgrowth was observed when oliogodendroglial cells were cultured in
the presence of Fumonisin B1, an inhibitor of sphingolipid synthesis
that prevents the formation of rafts. Because ligation of the cell
adhesion molecule F3 on oligodendrocytes leads to activation of Fyn
kinase localized in rafts, these findings suggest that recruitment of
Tau and Tubulin to activated Fyn kinase in rafts is an important step
in the initiation of myelination.
Key words:
myelination; oligodendrocytes; Fyn kinase; cytoskeleton; Tau; glycosphingolipid-rich rafts
Copyright © 2002 Society for Neuroscience 0270-6474/02/223698-10$05.00/0
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