title: Stabilization of exocytosis by dynamic F-actin coating of zymogen granules in pancreatic acini.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nemoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kojima
authors.forename: Akihiro
authors.initials: A
authors.lastname: Oshima
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Bito
authors.forename: Haruo
authors.initials: H
authors.lastname: Kasai
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D005089:Exocytosis; D051379:Mice; D010179:Pancreas / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D000199:Actins