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The Journal of Neuroscience, May 15, 2000, 20(10):3513-3521
Retroviral Inhibition of cAMP-Dependent Protein Kinase Inhibits
Myelination But Not Schwann Cell Mitosis Stimulated by Interaction with
Neurons
Douglas G.
Howe1 and
Ken D.
McCarthy1, 2
1 The Curriculum in Neurobiology and the
2 Department of Pharmacology, The University of North
Carolina, Chapel Hill, North Carolina 27599
Schwann cells are the myelinating glia of the peripheral nervous
system. Neuron-Schwann cell contact profoundly affects several aspects
of Schwann cell phenotype, including stimulation of mitosis and myelin
formation. Many reports suggest that neuronal contact exerts this
influence on Schwann cells by elevating Schwann cell cAMP and
activating cAMP-dependent protein kinase A (PKA). To elucidate
the importance of Schwann cell PKA in neuronal stimulation of Schwann
cell mitosis and myelination, the gene encoding the PKA inhibitory
protein RI AB or PKIEGFP was delivered to Schwann cells using
retroviral vectors. PKA inhibitory retroviral vectors effectively
blocked forskolin-stimulated Schwann cell mitosis and morphological
change, demonstrating the ability of the vectors to inhibit PKA in
infected Schwann cells. Treatment of dorsal root ganglia
neuron-Schwann cell cocultures with H-89 (10 µM) or
KT5720 (1-10 µM), chemical inhibitors selective for PKA,
significantly inhibited neuronal stimulation of Schwann cell mitosis.
In contrast, retrovirus-mediated inhibition of Schwann cell PKA had no
effect on the ability of neurons to stimulate Schwann cell mitosis.
However, markedly fewer myelin segments were formed by Schwann cells
expressing PKA inhibitory proteins compared with controls. These
results suggest that activation of Schwann cell PKA is required for
myelin formation but not for Schwann cell mitosis stimulated by
interaction with neurons.
Key words:
PKA; PKI; RIAB; retrovirus; GFP; Schwann; neuron-glial interaction; myelin; mitosis
Copyright © 2000 Society for Neuroscience 0270-6474/00/20103513-09$05.00/0
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