Stabilization of exocytosis by dynamic F-actin coating of zymogen granules in pancreatic acini.
Reorganization of F-actin in the apical region of mouse pancreatic acinar cells during Ca(2+)-dependent exocytosis of zymogen granules was investigated by two-photon excitation microscopy with intact acini. Granules were rapidly coated with F-actin in response to either agonist stimulation or photolysis of a caged-Ca(2+) compound. Such F-actin coating occurred exclusively at the surface of granules undergoing exocytosis and was prevented either by latrunculin-A, which inhibits actin polymerization, or by Clostridium botulinum exoenzyme C3, which inhibits the small GTPase Rho. Latrunculin-A or exoenzyme C3 also triggered the formation of vacuoles in acinar cells, a characteristic of acute pancreatitis. Stimulation of acini with high concentrations of cholecystokinin, which cause acute pancreatitis in mice, also impaired the F-actin coating of granules and induced vacuole formation. Latrunculin-A reduced the latency to exocytosis but did not affect the total number of exocytic events, suggesting that F-actin slows and further stabilizes exocytosis by facilitating F-actin coating. Rho-dependent F-actin coating of granule membranes thus stabilizes exocytic structures and is necessary for physiological progression of sequetial compound exocytosis in the exocrine pancreas and for prevention of acute pancreatitis.
Nemoto
Tomomi
T
Department of Cell Physiology, National Institute for Physiological Sciences, and Graduate University of Advanced Studies, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan.
Kojima
Tatsuya
T
Oshima
Akihiro
A
Bito
Haruhiko
H
Kasai
Haruo
H
D000199:Actins / Q000378:metabolism*; D000818:Animals; D005089:Exocytosis; D051379:Mice; D010179:Pancreas / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
D000199:Actins