Skip to main content
PMC home page
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;8(1):1–21. doi: 10.1111/j.1582-4934.2004.tb00255.x

Discovery of the Porosome: revealing the molecular mechanism of secretion and membrane fusion in cells

B P Jena 1,✉
PMCID: PMC6740243  PMID: 15090256

Abstract

Secretion and membrane fusion are fundamental cellular processes involved in the physiology of health and disease. Studies within the past decade reveal the molecular mechanism of secretion and membrane fusion in cells. Studies reveal that membrane‐bound secretory vesicles dock and fuse at porosomes, which are specialized plasma membrane structures. Swelling of secretory vesicles result in a build‐up of intravesicular pressure, which allows expulsion of vesicular contents. The discovery of the porosome, its isolation, its structure and dynamics at nm resolution and in real time, its biochemical composition and functional reconstitution, are discussed. The molecular mechanism of secretory vesicle fusion at the base of porosomes, and vesicle swelling, have been resolved. With these findings a new understanding of cell secretion has emerged and confirmed by a number of laboratories.

Keywords: porosome, cell secretion, membrane fusion, SNAREs, vesicle swelling

References

  • 1. Monck J.R., Oberhauser A.F., Fernandez J.M., The exocytotic fusion pore interface: a model of the site of neurotransmitter release, Mol. Memb. Biol., 12: 151–156, 1995. [DOI] [PubMed] [Google Scholar]
  • 2. Schneider S.W., Sritharan K.C., Geibel J.P., Oberleithner H., Jena B.P., Surface dynamics in living acinar cells imaged by atomic force microscopy: identification of plasma membrane structures involved in exocytosis, Proc. Natl. Acad. Sci. USA, 94: 316–321, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3. Cho S.‐J., Quinn A.S., Stromer M.H., Dash S., Cho J., Taatjes D.J., Jena B.P., Structure and dynamics of the fusion pore in live cells, Cell Biol. Int., 26: 35–42, 2002. [DOI] [PubMed] [Google Scholar]
  • 4. Cho S.‐J., Jeftinija K., Glavaski A., Jeftinija S., Jena B.P., Anderson L.L., Structure and dynamics of the fusion pores in live GH‐secreting cells revealed using atomic force microscopy, Endocrinology, 143: 1144–1148, 2002. [DOI] [PubMed] [Google Scholar]
  • 5. Cho S.‐J., Wakade A., Pappas G.D., Jena B.P., New structure involved in transient membrane fusion and exocytosis, New York Acad. Sci., 971: 254–256, 2002. [DOI] [PubMed] [Google Scholar]
  • 6. Tojima T., Yamane Y., Takagi H., Takeshita T., Sugiyama T., Haga H., Kawabata K., Ushiki T., Abe K., Yoshioka T., Ito E., Three‐dimensional characterization of interior structures of exocytotic apertures of nerve cells using atomic force microscopy, Neuroscience, 101: 471–481, 2000. [DOI] [PubMed] [Google Scholar]
  • 7. Gaisano H.Y., Sheu L., Wong P.P., Klip A., Trimble W.S., SNAP‐23 is located in the basolateral plasma membrane of rat pancreatic acinar cells, FEBS Lett., 414: 298–302, 1997. [DOI] [PubMed] [Google Scholar]
  • 8. Jena B.P., Cho S‐J., Jeremic A., Stromer M.H., Abu‐Hamdah R., Structure and composition of the fusion pore, Biophys. J., 84: 1337–1343, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Rothman J.E., Mechanism of intracellular protein transport, Nature, 372: 55–63, 1994. [DOI] [PubMed] [Google Scholar]
  • 10. Weber T., Zemelman B.V., McNew J.A., Westerman B., Gmachl M., Parlati F., Sollner T.H., Rothman J.E., SNAREpins: minimal machinery for membrane fusion, Cell, 92: 759–772, 1988. [DOI] [PubMed] [Google Scholar]
  • 11. Jeremic A.M., Kelly M., Cho S‐J., Stromer M.H., Jena B.P., Reconstituted fusion pore, Biophys. J., 85: 2035–2043, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Cho S.‐J., Kelly M., Rognlien K.T., Cho J., Hoerber J.K.H., Jena B.P., SNAREs in opposing bilayers interact in a circular array to form conducting pores, Biophys. J., 83: 2522–2527, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Bennett V., Spectrin‐based membrane skeleton: a multipotential adaptor between plasma membrane and cytoplasm, Physiol. Rev., 70: 1029–1065, 1990. [DOI] [PubMed] [Google Scholar]
  • 14. Faigle W., Colucci‐Guyon E., Louvard D., Amigorena S., Galli T., Vimentin filaments in fibroblasts are a reservoir for SNAP‐23, a component of the membrane fusion machinery, Mol. Biol. Cell., 11: 3485–3494, 2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Goodson H.V., Valetti C., Kreis T.E., Motors and membrane traffic, Curr. Opin. Cell Biol., 9: 18–28, 1997. [DOI] [PubMed] [Google Scholar]
  • 16. Nakano M., Nogami S., Sato S., Terano A., Shirataki H., Interaction of syntaxin with α‐fodrin, a major component of the submembranous cytoskeleton, Biochem. Biophys. Res. Commun., 288: 468–475, 2001. [DOI] [PubMed] [Google Scholar]
  • 17. Ohyama A., Komiya Y., Igarashi M., Globular tail of myosin‐V is bound to vamp/synaptobrevin, Biochem. Biophys. Res. Commun., 280: 988–991, 2001. [DOI] [PubMed] [Google Scholar]
  • 18. Prekereis R., Terrian D.M., Brain myosin V is a synaptic vesicle‐associated motor protein: evidence for a Ca2+‐ dependent interaction with the synaptobrevin‐synaptophysin complex, J. Cell Biol., 137: 1589–1601, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Jeong E.‐H., Webster P., Khuong C.Q., Sattar A.K.M.A., Satchi M., Jena B.P., The native membrane fusion machinery in cells, Cell Biol. Int., 22: 657–670, 1998. [DOI] [PubMed] [Google Scholar]
  • 20. Hanson P.I., Roth R., Morisaki H., Jahn R., Heuser J.E., Structure and conformational changes in NSF and its membrane receptor complexes visualized by quickfreeze/deep‐etch electron microscopy, Cell, 90: 523–535, 1997. [DOI] [PubMed] [Google Scholar]
  • 21. Sutton R.B., Fasshauer D., Jahn R., Brunger A.T., Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution, Nature, 395: 347–353, 1998. [DOI] [PubMed] [Google Scholar]
  • 22. Coorssen J.R., Blank P.S., Tahara M., Zimmerberg J., Biochemical and functional studies of cortical vesicle fusion: the SNARE complex and Ca2+ sensitivity, J. Cell Biol., 143: 1845–1857, 1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Tahara M., Coorssen J.R., Timmers K., Blank P.S., Whalley T., Scheller R., et al., Calcium can disrupt the SNARE protein complex on sea urchin egg secretory vesicles without irreversibly blocking fusion, J. Biol. Chem., 273: 33667–33673, 1998. [DOI] [PubMed] [Google Scholar]
  • 24. Zimmerberg J., Blank P.S., Kolosova I., Cho M.S., Tahara M., Coorssen J.R., A stage‐specific preparation to study the Ca2+ ‐triggered fusion steps of exocytosis: rationale and perspectives, Biochimie, 82: 303–314, 2000. [DOI] [PubMed] [Google Scholar]
  • 25. Llinas R., Sugimori M., Silver R.B., Microdomains of high calcium concentration in a presynaptic terminal, Science, 256: 677–679, 1992. [DOI] [PubMed] [Google Scholar]
  • 26. Llinas R., Sugimori M., Silver R.B., Presynaptic calcium concentration microdomains and transmitter release, J. Physiol. Paris, 86: 135–138, 1992. [DOI] [PubMed] [Google Scholar]
  • 27. Sheng Z.H., Rettig J., Cook T., Catterall W.A., Calcium‐dependent interaction of N‐type calcium channels with the synaptic core complex, Nature, 379: 451–454, 1996. [DOI] [PubMed] [Google Scholar]
  • 28. Edwardson J.M., An S., Jahn R., The secretory granule protein syncollin binds to syntaxin in a Ca2+ ‐sensitive manner, Cell, 90: 325–333, 1997. [DOI] [PubMed] [Google Scholar]
  • 29. Sudhof T.C., Rizo J., Synaptotagmins: C2‐domain proteins that regulate membrane traffic, Neuron, 17: 379–388, 1996. [DOI] [PubMed] [Google Scholar]
  • 30. Jeremic A., Kelly M., Cho J.‐H., Cho S.‐J., Horber J.K.H., Jena B.P., Calcium drives fusion of SNARE‐apposed bilayers, Cell Biol. Int., 28: 19–31, 2004. [DOI] [PubMed] [Google Scholar]
  • 31. Jena B.P., Schneider S.W., Geibel J.P., Webster P., Oberleithner H., Sritharan K.C., Gi regulation of secretory vesicle swelling examined by atomic force microscopy, Proc. Natl. Acad. Sci. USA, 94: 13317–13322, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Cho S.‐J., Sattar A.K., Jeong E.H., Satchi M., Cho J.A., Dash S., Mayes M.S., Stromer M.H., Jena B.P., Aquaporin 1 regulates GTP‐induced rapid gating of water in secretory vesicles, Proc. Natl. Acad. Sci. USA, 99: 4720–4724, 2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Abu‐Hamdah R., Cho W.‐J., Cho S.‐J., Jeremic A., Kelly M., Ilie A.E., Jena B.P., Regulation of the water channel aquaporin‐1: isolation and reconstitution of the regulatory complex, Cell Biol. Int., 28: 7–17, 2004. [DOI] [PubMed] [Google Scholar]
  • 34. Alvarez de Toledo G., Fernandez‐Chacon R., Fernandez J.M., Release of secretory products during transient vesicle fusion, Nature, 363: 554–558, 1993. [DOI] [PubMed] [Google Scholar]
  • 35. Curran M.J., Brodwick M.S., Ionic control of the size of the vesicle matrix of beige mouse mast cells, J. Gen. Physiol., 98: 771–790, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Monck J. R., Oberhauser A.F., Alvarez de Toledo G., Fernandez J.M., Is swelling of the secretory granule matrix the force that dilates the exocytotic fusion pore Biophys. J., 59: 39–47, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Sattar A.K.M., Boinpally R., Stromer M.H., Jena B.P., Gαi3 in pancreatic zymogen granule participates in vesicular fusion, J. Biochemistry, 131: 815–820, 2002. [DOI] [PubMed] [Google Scholar]
  • 38. Fernandez J.M., Villalon M., Verdugo P., Reversible condensation of the mast cell secretory products in vitro , Biophys. J., 59: 1022–1027, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Cho S.‐J., Cho J., Jena B.P., The number of secretory vesicles remains unchanged following exocytosis, Cell Biol. Int., 26: 29–33, 2002. [DOI] [PubMed] [Google Scholar]
  • 40. Jena B.P., Fusion pore in live cells, NIPS, 17: 219–222, 2002. [DOI] [PubMed] [Google Scholar]
  • 41. Jena B.P., Fusion pore: structure and dynamics, J. Endocrinology, 176: 169–174, 2003. [DOI] [PubMed] [Google Scholar]
  • 42. Jena B.P., Exocytotic fusion: total or transient, Cell Biol. Int., 21: 257–259, 1997. [DOI] [PubMed] [Google Scholar]
  • 43. Lee J.‐S., Mayes M.S., Stromer M.H., Scanes C.G., Jeftinija S., Anderson L.L., Number of secretory vesicles in growth hormone cells of the pituitary remains unchanged after secretion, Exp. Biol. Med. (in press, 2004). [DOI] [PubMed] [Google Scholar]
  • 44. Lawson D., Fewtrell C., Gomperts B., Raff M., Antiimmunoglobulin induced histamine secretion by rat peritoneal mast cells studied by immuno ferritin electron microscopy, J. Exp. Med., 142: 391–402, 1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45. Taraska J.W., Perrais D., Ohara‐Imaizumi M., Nagamatsu S., Almers W., Secretory granules are recaptured largely intact after stimulated exocytosis in cultured endocrine cells, Proc. Natl. Acad. Sci. USA, 100: 2070–2075, 2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Aravanis A.M., Pyle J.L., Tsien R.W., Single synaptic vesicles fusing transiently and successively without loss of identity, Nature, 423: 643–647, 2003. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES