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Vol. 14, Issue 1, 93-106, January 2003

Long-Term Potentiation of Exocytosis and Cell Membrane Repair in Fibroblasts

Tatsuru Togo,^* Janet M. Alderton,^* and Richard A. Steinhardt

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.

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^* Present address: Misaki Marine Biological Station, University of Tokyo, Misaki, Miura, Kanagawa 238-0225, Japan.

Corresponding author. E-mail address: rsteinha{at}socrates.berkeley.edu.

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Molecular Biology of the Cell
Vol. 14, 93-106, January 2003
Copyright © 2003 by The American Society for Cell Biology

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