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Volume 17, Number 23,
Issue of December 1, 1997
pp. 8955-8963
Inhibition of Axonal Growth by Brefeldin A in Hippocampal Neurons
in Culture
Received July 2, 1997; revised Aug. 29, 1997; accepted Sept. 16, 1997.
Mark Jareb and
Gary Banker
Department of Neuroscience, University of Virginia School of
Medicine, Charlottesville, Virginia 22908
The outgrowth of neuronal processes involves a great increase in
the surface area of the cell. The supply of membrane material necessarily must be coordinated with the demands for neurite growth. The selective growth of only one or two neurites at any given time
during the development of polarity raises the possibility that the
production of materials by the soma is limiting for growth (; ; ). To examine
the role of the availability of membrane components during the
development of polarity and axonal elongation, we treated neurons with
brefeldin A, an antibiotic that disrupts the trafficking of vesicles
from the Golgi complex to the plasma membrane. Treatment with brefeldin
A (1 µg/ml) inhibited axonal growth within 0.5 hr; in unpolarized
cells it prevented the formation of an axon. These results indicate
that the availability of membrane components of Golgi-derived vesicles
is required for axonal growth and hence the development of polarity.
Inhibitors of protein and RNA synthesis also blocked axonal growth and
the development of polarity, but over a much slower time course. This
suggests that the full complement of proteins and mRNAs required for
the initial development of polarity is present for several hours before
polarity is actually established.
Key words:
polarity;
neurite outgrowth;
hippocampal neurons;
brefeldin A;
Golgi complex;
axonal transport
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