Vacuolin-1-modulated exocytosis and cell resealing in mast cells |
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| Authors: | Gouse M Shaik Lubica Dráberová Petr Heneberg Petr Dráber |
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| Institution: | 1. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;2. Framingham Heart Study, Framingham, MA, USA;3. Cardiovascular Division, Brigham and Women''s Hospital, Harvard Medical School, Boston, MA, USA;4. Department of Mathematics and Statistics, Boston University, Boston, MA, USA;5. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;6. Genzyme Corporation, Cambridge, MA, USA;7. Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;8. Center for Population Studies, National Heart, Lung, & Blood Institute, Bethesda, MD, USA;9. Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA;10. Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;11. Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL, USA;12. Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA;1. Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, China;2. Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, China;3. Research Center for Clinical and Translational Medicine, The 302nd Hospital of PLA, Beijing, China;4. Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China;1. The Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China;2. Sol Sherry Thrombosis Research Center, Division of Hematology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA;3. Division of Hematology, Children''s Hospital of Philadelphia, Philadelphia, PA;4. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;5. Center For Advanced Proteomics Research, New Jersey Medical School, Rutgers University, Newark, NJ;6. Department of Biochemistry and Molecular and Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai, China;1. Department of Neurosurgery, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel;2. Department of Neurology, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel;3. Department of Neurology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA;1. Centre for Quantum Technologies, National University of Singapore, 3 Science Drive 2, 117543 Singapore, Singapore;2. Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań, Poland;3. ARC Centre of Excellence for Particle Physics at the Terascale, School of Physics, The University of Melbourne, Melbourne, Victoria 3010, Australia;4. Department of Physics, National University of Singapore, 2 Science Drive 3, 117542 Singapore, Singapore;1. Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, 430074, PR China;2. National Center for Magnetic Resonance in Wuhan, Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071, PR China;3. Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China |
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| Abstract: | The small chemical vacuolin-1 induces rapid formation of large vacuoles in various cell types. In epithelial cells, vacuolin-1 has been shown to inhibit Ca2+ ionophore-induced exocytosis depending on experimental conditions used but had no effect on repair of damaged membranes. However, it is not known whether vacuolin-1 could inhibit exocytosis induced by immunoreceptor triggering in professional secretory cells and whether there is any correlation between effect of vacuolin-1 on exocytosis and membrane repair in such cells. Here we show that in rat basophilic leukemia (RBL-2H3) cells activated by the high-affinity IgE receptor (FcεRI) triggering vacuolin-1 enhanced exocytosis. Under identical conditions of activation, vacuolin-1 inhibited exocytosis in mouse bone marrow-derived mast cells (BMMCs). This inhibition was not reflected by decreased phosphorylation of the FcεRI α and β subunits, linker for activation of T cells, non-T cell activation linker, Akt and MAP kinase Erk, and uptake of extracellular Ca2+, indicating that early activation events are not affected. In both cell types vacuolin-1 led to formation of numerous vacuoles, a process which was inhibited by bafilomycin A1, an inhibitor of vacuolar H+-ATPase. Thapsigargin- or Ca2+ ionophore A23187-induced exocytosis also showed different sensitivity to the inhibitory effect of vacuolin-1. Pretreatment of the cells with vacuolin-1 followed by permeabilization with bacterial toxin streptolysin O enhanced Ca2+-dependent repair of plasma membrane lesions in RBL-2H3 cells but inhibited it in BMMCs. Our data indicate that lysosomal exocytosis exhibits different sensitivity to vacuolin-1 depending on the cell type analyzed and mode of activation. Furthermore, our results support the concept that lysosomal exocytosis is involved in the repair of injured plasma membranes. |
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