Porosome: the Universal Molecular Machinery for Cell Secretion

  • Jena, Bhanu P. (Department of Physiology, Wayne State University School of Medicine)
  • Received : 2008.11.06
  • Accepted : 2008.11.10
  • Published : 2008.12.31


Porosomes are supramolecular, lipoprotein structures at the cell plasma membrane, where membrane-bound secretory vesicles transiently dock and fuse to release inravesicular contents to the outside during cell secretion. The mouth of the porosome opening to the outside, range in size from 150 nm in diameter in acinar cells of the exocrine pancreas, to 12 nm in neurons, which dilates during cell secretion, returning to its resting size following completion of the process. In the past decade, the composition of the porosome, its structure and dynamics at nm resolution and in real time, and its functional reconstitution into artificial lipid membrane, have all been elucidated. In this mini review, the discovery of the porosome, its structure, function, isolation, chemistry, and reconstitution into lipid membrane, the molecular mechanism of secretory vesicle swelling and fusion at the base of porosomes, and how this new information provides a paradigm shift in our understanding of cell secretion, is discussed.


cell secretion;membrane fusion;porosome


Supported by : National Institutes of Health (USA), National Science Foundation (USA), Wayne State University


  1. Bako, I., Hutter, J., and Palinkas, G. (2002). Car-Parrinello molecular dynamics simulation of the hydrated calcium ion. J. Chem. Phys. 117, 9838-9843 https://doi.org/10.1063/1.1517039
  2. Cho, S.J., Wakade, A., Pappas, G.D., and Jena, B.P. (2002d). New structure involved in transient membrane fusion and exocytosis. Ann. NY Acad. Sci. 971, 254-256 https://doi.org/10.1111/j.1749-6632.2002.tb04471.x
  3. Cho, S.-J., Sattar, AK, Jeong, E.H., Satchi, M., Cho, J., Dash, S., Mayes, M.S., Stromer, M.H., and Jena, B.P. (2002f). Aquaporin 1 regulates GTP-induced rapid gating of water in secretory vesicles. Proc. Natl. Acad. Sci. USA 99, 4720-4724
  4. Cho, W.J., Ren, G., and Jena, B.P. (2008). EM 3D contourmaps provide protein assembly at the nanoscale within the neuronal porosome complex. J. Microscopy 232, 106-111 https://doi.org/10.1111/j.1365-2818.2008.02088.x
  5. Gaisano, H.Y., Sheu, L., Wong, P.P., Klip, A., and Trimble, w'S. (1997). SNAP-23 is located in the basolateral plasma membrane of rat pancreatic acinar cells. FEBS Lett. 414, 298-302 https://doi.org/10.1016/S0014-5793(97)01013-2
  6. Goodson, HV., Valetti, C., and Kreis, TE. (1997). Motors and membrane traffic. Curr. Opin. Cell BioI. 9, 18-28 https://doi.org/10.1016/S0955-0674(97)80147-0
  7. Jena, B.P. (2004). Discovery of the Porosome: revealing the molecular mechanism of secretion and membrane fusion in cells. J. Cell. Mol. Med. 8, 1-21 https://doi.org/10.1111/j.1582-4934.2004.tb00255.x
  8. Jena, B.P. (2005). Molecular machinery and mechanism of cell secretion. Exp. BioI. Med. 230, 307-319 https://doi.org/10.1177/153537020523000504
  9. Jeremic, A, Cho, w'J., and Jena, B.P. (2004b). Membrane fusion: what may transpire at the atomic level. J. BioI. Phys. Chern. 4, 139-142
  10. Jeremic, A, Cho, w'J., and Jena, B.P. (2005). Involvement of water channels in synaptic vesicle swelling. Exp. BioI. Med. 230, 674-680 https://doi.org/10.1177/153537020523000910
  11. Ohyama, A, Komiya, Y., and Igarashi, M. (2001). Globular tail of myosin-V is bound to vamp/synaptobrevin. Biochem. Biophys. Res. Commun. 280, 988-991 https://doi.org/10.1006/bbrc.2001.4236
  12. Abu-Hamdah, R., Cho, W.J., Cho, S.-J., Jeremic, A., Kelly, M., Ilie, A.E., and Jena, B.P. (2004). Regulation of the water channel aquaporin-1: isolation and reconstitution of the regulatory complex. Cell Biol. Int. 28, 7-17 https://doi.org/10.1016/j.cellbi.2003.11.003
  13. Jena, B.P., Schneider, SW., Geibel, J.P., Webster, P., Oberleithner, H., and Sritharan, KC. (1997). G; regulation of secretory vesicle swelling examined by atomic force microscopy. Proc. Natl. Acad. Sci. USA 94,13317-13322
  14. Cho, W.J., Jeremic, A., Rognlien, K1., Zhvania, M.G., Lazrishvili, I., Tamar, B., and Jena, B.P. (2004). Structure, isolation, composition and reconstitution of the neuronal fusion pore. Cell BioI. Int. 28,699-708 https://doi.org/10.1016/j.cellbi.2004.07.004
  15. Jeremic, A, Kelly, M., Cho, S.-J., Stromer, M.H., and Jena, B.P. (2003). Reconstituted fusion pore. Biophys. J. 85, 2035-2043 https://doi.org/10.1016/S0006-3495(03)74631-1
  16. Jena, B.P. (2007). Secretion machinery at the cell plasma membrane. Curr. Opin. Struct. BioI. 17, 437-443 https://doi.org/10.1016/j.sbi.2007.07.002
  17. Cho, S.-J., Quinn, A.S., Stromer, M.H., Dash, S., Cho, J., Taatjes, D.J., and Jena, B.P. (2002a). Structure and dynamics of the fusion pore in live cells. Cell Biol. Int. 26, 35-42 https://doi.org/10.1006/cbir.2001.0849
  18. Jeremic, A, Kelly, M., Cho, J., Cho, S.-J., Harber, J.K., and Jena, B.P. (2004a). Calcium drives fusion of SNARE-apposed bilayers. Cell Bioi .Int. 28, 19-31 https://doi.org/10.1016/j.cellbi.2003.11.004
  19. Lawson, D., Fewtrell, C., Gomperts, B., and Raff, M. (1975). Antiimmunoglobulin-induced histamine secretion by rat peritoneal mast cells studied by immunoferritin electron microscopy. J. Exp. Med. 142,391-401 https://doi.org/10.1084/jem.142.2.391
  20. Wilson, OW., Whiteheart, SW., Wiedmann, M., Brunner, M., and Rothman, JE. (1992). A multisubunit particle implicated in membrane fusion. J. Cell BioI. 117,531-538 https://doi.org/10.1083/jcb.117.3.531
  21. Cho, S.-J., Kelly, M., Rognlien, K.T., Cho, J., Harber, J.K., and Jena, B.P. (2002c). SNAREs in opposing bilayers interact in a circular array to form conducting pores. Biophys. J. 83, 2522-2527 https://doi.org/10.1016/S0006-3495(02)75263-6
  22. Kelly, M., Cho, vis, Jeremic, A, Abu-Hamdah, R., and Jena, B.P. (2004). Vesicle swelling regulates content expulsion during secretion. Cell BioI. Int. 28, 709-716 https://doi.org/10.1016/j.cellbi.2004.07.005
  23. Oyler, GA, Higgins, GA, Hart, RA, Battenberg, E., Billingsley, M., Bloom, FE., and Wilson, M.C. (1989). The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations. J. Cell BioI. 109,3039-3052 https://doi.org/10.1083/jcb.109.6.3039
  24. Trimble, W.S., Cowan, OW., and Scheller, R.H. (1988). VAMP-1: A synaptic vesicle-associated integral membrane protein. Proc. Natl. Acad. Sci. USA 85, 4538-4542
  25. Faigle, W., Colucci-Guyon, E., Louvard, D., Amigorena, S., and Galli, 1. (2000). Vimentin filaments in fibroblasts are a reservoir for SNAP-23, a component of the membrane fusion machinery. Mol. BioI. Cell 11,3485-3494 https://doi.org/10.1091/mbc.11.10.3485
  26. Cho, W.J., Jeremic, A., and Jena, B.P. (2005b). Direct interaction between SNAP-23 and L-type calcium channel. J. Cell. Mol. Med. 9, 380-386 https://doi.org/10.1111/j.1582-4934.2005.tb00363.x
  27. Bennett, V. (1990). Spectrin-based membrane skeleton: a multipotential adaptor between plasma membrane and cytoplasm. Physiol. Rev 70, 1029-1065 https://doi.org/10.1152/physrev.1990.70.4.1029
  28. Jeremic, A, Quinn, AS., Cho, W.J., Taatjes, D.J., and Jena, B.P. (2006). Energy-dependent disassembly of self-assembled SNARE complex: observation at nanometer resolution using atomic force microscopy. J. Am. Chern. Soc. 128,26-27 https://doi.org/10.1021/ja056286v
  29. Potoff, J.J., Issa, Z., Manke, C.w', Jr., and Jena, B.P. (2008). Ca2+Dimethylphosphate complex formation: providing insight into Ca2+ mediated local dehydration and membrane fusion in cells. Cell BioI. Int. 32, 361-366 https://doi.org/10.1016/j.cellbi.2008.03.002
  30. Woodbury, D.J. (1999). Nystatin/ergosterol method for reconstituting ion channels into planar lipid bilayers. Methods Enzymol. 294, 319-339 https://doi.org/10.1016/S0076-6879(99)94020-X
  31. Bennett, M.K., Calakos, N., and Schller, R.H. (1992). Syntaxin: A synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 257, 255-259 https://doi.org/10.1126/science.1321498
  32. Malhotra, V., Orci, L., Glick, B.S., Block, M.R., and Rothman, J.E. (1988). Role of an N-ethylmaleimide-sensitive transport component in promoting fusion of transport vesicles with cisternae of the Golgi stack. Cell 54, 221-227 https://doi.org/10.1016/0092-8674(88)90554-5
  33. Cohen, F.S., and Niles, W.D. (1993). Reconstituting channels into planar membranes: a conceptual framework and methods for fusing vesicles to planar bilayer phospholipid membranes. Methods Enzymol. 220, 50-68 https://doi.org/10.1016/0076-6879(93)20073-C
  34. Woodbury, D.J., and Miller, C. (1990). Nystatin-induced liposome fusion. A versatile approach to ion channel reconstitution into planar bilayers. Biophys. J. 58, 833-839 https://doi.org/10.1016/S0006-3495(90)82429-2
  35. Jena, B.P., Cho, S.-J., Jeremic, A., Stromer, M.H., and AbuHamdah, R. (2003). Structure and composition of the fusion pore. Biophys. J. 84,1-7 https://doi.org/10.1016/S0006-3495(03)74827-9
  36. Cho, S.-J., Jeftinija, K., Glavaski, A., Jeftinija, S., Jena, B.P., and Anderson, L.L. (2002b). Structure and dynamics of the fusion pores in live GH-secreting cells revealed using atomic force microscopy. Endocrinology 143, 1144-1148 https://doi.org/10.1210/en.143.3.1144
  37. Kelly, M.L., and Woodbury, D.J. (1996). Ion channels from synaptic vesicle membrane fragments reconstituted into lipid bilayers. Biophys. J. 70,2593-2599 https://doi.org/10.1016/S0006-3495(96)79830-2
  38. Schneider, S.w', Sritharan, K.C., Geibel, J.P., Oberleithner, H., and Jena, B.P. (1997). 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
  39. Nakano, M., Nogami, S., Sato, S., Terano, A, and Shirataki, H. (2001). Interaction of syntaxin with a-todrin, a major component of the submembranous cytoskeleton. Biochem. Biophys. Res. Commun. 288, 468-475 https://doi.org/10.1006/bbrc.2001.5795
  40. Plattner, H., Atalejo, AR., and Neher, E. (1997). Ultrastructural organization of bovine chromaffin cell cortex-analysis by cryofixation and morphometry of aspects pertinent to exocytosis. J. Cell BioI. 139,1709-1717 https://doi.org/10.1083/jcb.139.7.1709
  41. Cho, W.J., Jeremic, A. Jin, H., Ren, G., and Jena, B.P. (2007). Neuronal fusion pore assembly requires membrane cholesterol. Cell BioI. Int. 31, 1301-1308 https://doi.org/10.1016/j.cellbi.2007.06.011
  42. Cho, w'J., and Jena, B.P. (2007). N-ethymaleimide sensitive factor is a right-handed molecular motor. J. Biomed. Nanotech. 3, 209-211 https://doi.org/10.1166/jbn.2007.026
  43. Jeong, E.-H., Webster, P., Khuong, C.O., Abdus Sattar, A.K, Satchi, M., and Jena, B.P. (1999). The native membrane fusion machinery in cells. Cell BioI. Int. 22, 657-670
  44. Cho, W.J., Jeremic, A., and Jena, B.P. (2005a). Size of supramolecular SNARE complex membrane-directed self-assembly. J. Am. Chem. Soc. 127,10156-10157 https://doi.org/10.1021/ja052442m
  45. Cho, S.-J., Cho, J., and Jena, B.P. (2002e). The number of secretory vesicles remains unchanged flowing exocytosis. Cell BioI. Int. 26, 29-33 https://doi.org/10.1006/cbir.2001.0848
  46. Cook, J.D., Cho, W.J., Stemmler, T.L., and Jena, B.P. (2008). Circular dichroism (CD) spectroscopy of the assembly and disassembly of SNAREs: the proteins involved in membrane fusion in cells. Chem .Phys. Lett. 462, 6-9 https://doi.org/10.1016/j.cplett.2008.07.043