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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Xu, X. Kwiatkowska, K. Muallem, S. Yin, H. L. |
| Description | Author Affiliation: Muallem S ( Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.) |
| Abstract | Although the actin cytoskeleton has been implicated in vesicle trafficking, docking and fusion, its site of action and relation to the Ca(2+)-mediated activation of the docking and fusion machinery have not been elucidated. In this study, we examined the role of actin filaments in regulated exocytosis by introducing highly specific actin monomer- binding proteins, the beta-thymosins or a gelsolin fragment, into streptolysin O-permeabilized pancreatic acinar cells. These proteins had stimulatory and inhibitory effects. Low concentrations elicited rapid and robust exocytosis with a profile comparable to the initial phase of regulated exocytosis, but without raising [Ca2+], and even when [Ca2+] was clamped at low levels by EGTA. No additional cofactors were required. Direct visualization and quantitation of actin filaments showed that beta-thymosin, like agonists, induced actin depolymerization at the apical membrane where exocytosis occurs. Blocking actin depolymerization by phalloidin or neutralizing beta- thymosin by complexing with exogenous actin prevented exocytosis. These findings show that the cortical actin network acts as a dominant negative clamp which blocks constitutive exocytosis. In addition, actin filaments also have a positive role. High concentrations of the actin depolymerizing proteins inhibited all phases of exocytosis. The inhibition overrides stimulation by agonists and all downstream effectors tested, suggesting that exocytosis cannot occur without a minimal actin cytoskeletal structure. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 4 |
| Volume Number | 128 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 1995-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Actins Metabolism Cytoskeleton Exocytosis Physiology Pancreas Animals Calcium Carbachol Pharmacology Cell Membrane Permeability Gelsolin Guanosine 5'-O-(3-Thiotriphosphate) Inositol 1,4,5-Trisphosphate Cytology Drug Effects Polymers Sincalide Streptolysins Tetradecanoylphorbol Acetate Thymosin Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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