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Vol. 13, Issue 1, 12-24, January 2002
Actin-binding Site Is Important for Neurite
Outgrowth during Neuronal Differentiation
Department of Laboratory Medicine, Molecular Medicine, Lund
University, Malmö University Hospital, 205 02 Malmö, Sweden
We have previously shown that protein kinase C
(PKC
) induces
neurite outgrowth via its regulatory domain and independently of its
kinase activity. This study aimed at identifying mechanisms regulating
PKC
-mediated neurite induction. We show an increased association of
PKC
to the cytoskeleton during neuronal differentiation. Furthermore, neurite induction by overexpression of full-length PKC
is suppressed if serum is removed from the cultures or if an
actin-binding site is deleted from the protein. A peptide corresponding to the PKC
actin-binding site suppresses neurite outgrowth during neuronal differentiation and outgrowth elicited by PKC
overexpression. Neither serum removal, deletion of the actin-binding
site, nor introduction of the peptide affects neurite induction by the
isolated regulatory domain. Membrane targeting by myristoylation
renders full-length PKC
independent of both serum and the
actin-binding site, and PKC
colocalized with F-actin at the cortical
cytoskeleton during neurite outgrowth. These results demonstrate that
the actin-binding site is of importance for signals acting on PKC
in
a pathway leading to neurite outgrowth. Localization of PKC
to the
plasma membrane and/or the cortical cytoskeleton is conceivably
important for its effect on neurite outgrowth.
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