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Volume 16, Number 16,
Issue of August 15, 1996
pp. 4994-5003
Copyright ©1996 Society for Neuroscience
Neural Influence on Protein Kinase C Isoform Expression in
Skeletal Muscle
Received March 5, 1996; revised May 29, 1996; accepted May 30, 1996.
Lutz Hilgenberg,
Simone Yearwood,
Stuart Milstein, and
Kathryn Miles
Department of Anatomy and Cell Biology, The State University of New
York Health Science Center at Brooklyn, Brooklyn, New York 11203
Protein kinase C (PKC) is a family of enzymes involved in synapse
formation and signal transduction at the neuromuscular junction. Two
PKC isoforms, classical PKC and novel PKC , have been shown to
be enriched in skeletal muscle or localized to the endplate. We
examined the role of nerve in regulating the expression of these PKC
isoforms in rat skeletal muscle by denervating diaphragm muscle and
measuring PKC protein expression at various postoperative times. nPKC
protein levels decreased 65% after denervation, whereas cPKC levels increased 80% compared with control hemidiaphragms. These
results suggest that innervation regulates PKC and isoform
expression in skeletal muscle. To explore further how nerve regulates
PKC expression, we characterized PKC isoform expression in rat myotubes
deprived of neural input. Myoblast expression of nPKC was low, and
the increase in nPKC expression that occurred during
differentiation into myotubes resulted in levels of nPKC significantly below adult skeletal muscle. cPKC expression in
myoblasts increased during differentiation to levels that exceeded
expression in adult skeletal muscle. Coculturing myotubes with a
neuroblastoma X glioma hybrid clonal cell line (NG108-15) increased
nPKC expression, but not cPKC , suggesting that nPKC in
skeletal muscle and myotubes is regulated by nerve contact or by a
factor(s) provided by nerve. Treating myotubes with tetrodotoxin did
not affect either basal- or NG108-15 cell-stimulated nPKC expression. Together these results suggest that expression of nPKC in skeletal muscle is regulated by a transynaptic interaction with
nerve that specifically influences nPKC expression.
Key words:
protein kinase C;
cPKC ;
nPKC ;
neuromuscular junction;
NG108-15 cells;
denervation
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