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Published 3 September 2002. doi:10.1083/jcb1585iti3
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© The Rockefeller University Press, 0021-9525/2002/9/829 $5.00
The Journal of Cell Biology, Volume 158, Number 5, September 2, 2002 829-829


In This Issue

A zipper designed to snag


SNARE proteins zipper up during fusion.

In the current model of vesicle membrane fusion, a helical bundle formed by v- and t-SNARE proteins works like a zipper, drawing closed first at the membrane-distal end, and zipping up toward the membrane-proximal end of the bundle. On page 929, Melia et al. describe the first functional test of this model. Besides confirming that zippering occurs in the membrane-distal to membrane-proximal direction, the results uncover a new regulatory step in vesicle fusion.

The authors examined fusion between liposomes reconstituted with mammalian SNARE proteins and added peptides that bound to either the membrane-proximal COOH terminus or membrane-distal NH2 terminus of the t-SNARE. As predicted by the model, the NH2- directed peptides block initial contact between v- and t-SNARES and inhibit fusion, but, once zippering has started, fusion is resistant to these NH2-directed peptides. The COOH-directed peptides, however, dramatically increase the rate of fusion, a result not predicted by the model.

Melia et al. suggest that the COOH-directed peptides are affecting a previously unrecognized inherent regulatory switch in the t-SNARE, which they name the tC fusion switch. In its default state, the switch is off and pauses zippering at about the midpoint of the bundle. The right peptide, such as the COOH-directed peptides or perhaps a sequence from a regulatory protein, can structure the coil, turn the switch on, and accelerate fusion. {blacksquare}



Alan W. Dove

alanwdove{at}earthlink.net


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Related Article

Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins
Thomas J. Melia, Thomas Weber, James A. McNew, Lillian E. Fisher, Robert J. Johnston, Frank Parlati, Lara K. Mahal, Thomas H. Söllner, and James E. Rothman
J. Cell Biol. 2002 158: 929-940. [Abstract] [Full Text] [PDF]




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