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Vol. 14, Issue 1, 93-106, January 2003
Department of Molecular and Cell Biology, University of California,
Berkeley, California 94720-3200
We previously found that a microdisruption of the plasma membrane
evokes Ca2+-regulated exocytosis near the wound site, which
is essential for membrane resealing. We demonstrate herein that
repeated membrane disruption reveals long-term potentiation of
Ca2+-regulated exocytosis in 3T3 fibroblasts, which is
closely correlated with faster membrane resealing rates. This
potentiation of exocytosis is cAMP-dependent protein kinase A
dependent in the early stages (minutes), in the intermediate term
(hours) requires protein synthesis, and for long term (24 h) depends on
the activation of cAMP response element-binding protein (CREB). We were
able to demonstrate that wounding cells activated CREB within 3.5 h. In all three phases, the increase in the amount of exocytosis was
correlated with an increase in the rate of membrane resealing. However,
a brief treatment with forskolin, which is effective for short-term
potentiation and which could also activate CREB, was not sufficient to
induce long-term potentiation of resealing. These results imply that long-term potentiation by CREB required activation by another, cAMP-independent pathway.
Corresponding author. E-mail address:
rsteinha{at}socrates.berkeley.edu.
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