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Vol. 18, Issue 9, 3502-3511, September 2007

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Dynamic Regulation of the Large Exocytotic Fusion Pore in Pancreatic Acinar Cells

Olga Larina^*,, Purnima Bhat^,, James A. Pickett^*, Bradley S. Launikonis, Amit Shah^*, Wade A. Kruger, J. Michael Edwardson^*, and Peter Thorn

*Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, United Kingdom; and School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia

Submitted January 12, 2007; Revised June 12, 2007; Accepted June 20, 2007
Monitoring Editor: Tom U. Martin

Loss of granule content during exocytosis requires the opening of a fusion pore between the secretory granule and plasma membrane. In a variety of secretory cells, this fusion pore has now been shown to subsequently close. However, it is still unclear how pore closure is physiologically regulated and contentious as to how closure relates to granule content loss. Here, we examine the behavior of the fusion pore during zymogen granule exocytosis in pancreatic acinar cells. By using entry of high-molecular-weight dyes from the extracellular solution into the granule lumen, we show that the fusion pore has a diameter of 29–55 nm. We further show that by 5 min after granule fusion, many granules have a closed fusion pore with evidence indicating that pore closure is a prelude to endocytosis and that in granules with a closed fusion pore the chymotrypsinogen content is low. Finally, we show that latrunculin B treatment promotes pore closure, suggesting F-actin affects pore dynamics. Together, our data do not support the classical view in acinar cells that exocytosis ends with granule collapse. Instead, for many granules the fusion pore closes, probably as a transition to endocytosis, and likely involving an F-actin–dependent mechanism.

These authors contributed equally to this work.

Address correspondence to: Peter Thorn (p.thorn{at}uq.edu.au).

Abbreviations used: ACh, acetylcholine.