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. 1990 Mar 1;95(3):397–409. doi: 10.1085/jgp.95.3.397

Compound versus multigranular exocytosis in peritoneal mast cells

PMCID: PMC2216328  PMID: 2324701

Abstract

We have used the whole-cell patch-pipette technique to measure the step increases in the cell membrane capacitance (equivalent to the membrane area) caused by the fusion of secretory granules in degranulating murine mast cells. We have observed that up to 30% of the total membrane expansion caused by degranulation results from large fusion events that cannot be explained by the fusion of single secretory granules. These large events are observed mainly in the initial phase of a degranulation. We have developed a simple mathematical model for a mast cell to test whether these large events are caused by a stimulus- induced, granule-to-granule fusion that occurs before their exocytosis (multigranular exocytosis). Our results suggest that the large fusion events are caused by the exocytosis of granule aggregates that existed before stimulation and that are located at the cell's periphery. We propose a novel mechanism by which granule aggregates can be formed at the periphery of the cell. This mechanism relies on the ability of a transiently fused granule ("flicker") to fuse with more internally located granules in a sequential manner. This pattern may result in the formation of larger peripheral granules that later on can fuse with the membrane. The formation of peripheral granule aggregates may potentiate a subsequent secretory response.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alvarez de Toledo G., Fernandez J. M. The events leading to secretory granule fusion. Soc Gen Physiol Ser. 1988;43:333–344. [PubMed] [Google Scholar]
  2. Anderson P., Slorach S. A., Uvnäs B. Sequential exocytosis of storage granules during antigen-induced histamine release from sensitized rat mast cells in vitro. An electron microscopic study. Acta Physiol Scand. 1973 Jul;88(3):359–372. doi: 10.1111/j.1748-1716.1973.tb05465.x. [DOI] [PubMed] [Google Scholar]
  3. Bloom G. D., Haegermark O. Studies on morphological changes and histamine release induced by bee venom, n-decylamine and hypotonic solutions in rat peritoneal mast cells. Acta Physiol Scand. 1967 Dec;71(4):257–269. doi: 10.1111/j.1748-1716.1967.tb03733.x. [DOI] [PubMed] [Google Scholar]
  4. Breckenridge L. J., Almers W. Currents through the fusion pore that forms during exocytosis of a secretory vesicle. 1987 Aug 27-Sep 2Nature. 328(6133):814–817. doi: 10.1038/328814a0. [DOI] [PubMed] [Google Scholar]
  5. Breckenridge L. J., Almers W. Final steps in exocytosis observed in a cell with giant secretory granules. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1945–1949. doi: 10.1073/pnas.84.7.1945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chandler D. E., Bennett J. P., Gomperts B. Freeze-fracture studies of chemotactic peptide-induced exocytosis in neutrophils: evidence for two patterns of secretory granule fusion. J Ultrastruct Res. 1983 Feb;82(2):221–232. doi: 10.1016/s0022-5320(83)90055-2. [DOI] [PubMed] [Google Scholar]
  7. Chandler D. E., Kazilek C. J. Chemotactic peptide-induced exocytosis in neutrophils: granule fusion patterns depend on the source of messenger calcium. J Cell Sci. 1986 Jul;83:293–311. doi: 10.1242/jcs.83.1.293. [DOI] [PubMed] [Google Scholar]
  8. Dvorak A. M., Galli S. J., Morgan E., Galli A. S., Hammond M. E., Dvorak H. F. Anaphylactic degranulation of guinea pig basophilic leukocytes. I. Fusion of granule membranes and cytoplasmic vesicles formation and resolution of degranulation sacs. Lab Invest. 1981 Feb;44(2):174–191. [PubMed] [Google Scholar]
  9. Fernandez J. M., Neher E., Gomperts B. D. Capacitance measurements reveal stepwise fusion events in degranulating mast cells. 1984 Nov 29-Dec 5Nature. 312(5993):453–455. doi: 10.1038/312453a0. [DOI] [PubMed] [Google Scholar]
  10. Hammel I., Dvorak A. M., Peters S. P., Schulman E. S., Dvorak H. F., Lichtenstein L. M., Galli S. J. Differences in the volume distributions of human lung mast cell granules and lipid bodies: evidence that the size of these organelles is regulated by distinct mechanisms. J Cell Biol. 1985 May;100(5):1488–1492. doi: 10.1083/jcb.100.5.1488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hammel I., Lagunoff D., Bauza M., Chi E. Periodic, multimodal distribution of granule volumes in mast cells. Cell Tissue Res. 1983;228(1):51–59. doi: 10.1007/BF00206264. [DOI] [PubMed] [Google Scholar]
  12. Helander H. F., Bloom G. D. Quantitative analysis of mast cell structure. J Microsc. 1974 Apr;100(3):315–321. doi: 10.1111/j.1365-2818.1974.tb03943.x. [DOI] [PubMed] [Google Scholar]
  13. Henderson W. R., Chi E. Y. Ultrastructural characterization and morphometric analysis of human eosinophil degranulation. J Cell Sci. 1985 Feb;73:33–48. doi: 10.1242/jcs.73.1.33. [DOI] [PubMed] [Google Scholar]
  14. Joshi C., Fernandez J. M. Capacitance measurements. An analysis of the phase detector technique used to study exocytosis and endocytosis. Biophys J. 1988 Jun;53(6):885–892. doi: 10.1016/S0006-3495(88)83169-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kurihara H., Kitajima K., Senda T., Fujita H., Nakajima T. Multigranular exocytosis induced by phospholipase A2-activators, melittin and mastoparan, in rat anterior pituitary cells. Cell Tissue Res. 1986;243(2):311–316. doi: 10.1007/BF00251045. [DOI] [PubMed] [Google Scholar]
  16. Morgenstern E., Neumann K., Patscheke H. The exocytosis of human blood platelets. A fast freezing and freeze-substitution analysis. Eur J Cell Biol. 1987 Apr;43(2):273–282. [PubMed] [Google Scholar]
  17. Neher E., Marty A. Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6712–6716. doi: 10.1073/pnas.79.21.6712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Röhlich P., Anderson P., Uvnäs B. Electron microscope observations on compounds 48-80-induced degranulation in rat mast cells. Evidence for sequential exocytosis of storage granules. J Cell Biol. 1971 Nov;51(21):465–483. doi: 10.1083/jcb.51.2.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Zimmerberg J., Curran M., Cohen F. S., Brodwick M. Simultaneous electrical and optical measurements show that membrane fusion precedes secretory granule swelling during exocytosis of beige mouse mast cells. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1585–1589. doi: 10.1073/pnas.84.6.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]

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