Putting the clamps on membrane fusion: how complexin sets the stage for calcium-mediated exocytosis.
Three recent papers have addressed a long-standing question in exocytosis: how does a sudden calcium influx trigger a coordinated synchronous release in regulated exocytosis [Giraudo, C.G., Eng, W.S., Melia, T.J. and Rothman, J.E. (2006) A clamping mechanism involved in SNARE-dependent exocytosis. Science 313, 676-680; Schaub, J.R., Lu, X., Doneske, B., Shin, Y.K. and McNew, J.A. (2006) Hemifusion arrest by complexin is relieved by Ca(2+)-synaptotagmin I. Nat. Struct. Mol. Biol. 13, 748-750; Tang, J., Maximov, A., Shin, O.H., Dai, H., Rizo, J. and Sudhof, T.C. (2006) A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell 126, 1175-1187]? Using diverse approaches that include cell-free reconstitution of the membrane fusion machinery and in vivo manipulation of fusogenic proteins, these groups have established that the complexin proteins are fusion clamps. By arresting vesicle secretion just prior to fusion, complexin primes select vesicles for a fast, synchronous response to calcium.
Melia
Thomas J
TJ
Columbia University, Department of Physiology and Cellular Biophysics, 1150 Saint Nicholas Avenue, New York, NY 10032, USA tm2176@columbia.edu
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D050600:SNARE Proteins / Q000737:chemistry / Q000378:metabolism; D050857:Synaptotagmins / Q000737:chemistry / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; C095992:complexin I; D050857:Synaptotagmins; D002118:Calcium