The addition of iSNAREs (red) inhibits normally active SNARE complexes.

Two membranes fuse into one through the action of SNARE proteins. As only particular combinations of t-SNAREs (on the target membrane) and v-SNAREs (on the vesicle) will cause fusion between bilayers, restricting their localization promotes fusion in the right place. On page 79, Varlamov et al. add a new layer to the regulation by showing that some SNAREs actually block fusion that would otherwise occur in the wrong place.

SNARE specificity forms two mutually exclusive systems in the Golgi—one enriched at the cis and one at the trans face of the Golgi. The concentration of cis t-SNAREs at the cis face of the Golgi, where trans t-SNAREs are scarce, helps prevent vesicles bearing trans v-SNAREs from fusing there and vice versa. But even an imperfect distribution of t-SNAREs may be offset by inhibitory SNAREs (i-SNAREs), based on the new results.

The authors found that some trans-Golgi SNAREs inhibit fusion reactions by cis-Golgi SNAREs and vice versa. At least some of these iSNAREs block fusion by substituting for one of the SNARE subunits of the fusion-competent complex. Most SNARE combinations that will not cause fusion do not form a complex. However, a few nonfusogenic complexes have been seen to form in vitro. Varlamov et al. suggest that these unusual complexes are insurance against unwanted fusion events.

To test their theory, the group recreated the SNARE composition of the Golgi compartments in vitro using liposomes and yeast versions of mammalian SNAREs at concentrations mimicking those seen in vivo. Vesicles containing either cis- or trans-Golgi SNAREs accurately fused with the cis- or trans-Golgi liposomes, respectively. But if the authors removed i-SNAREs from the recreated Golgi, vesicle targeting was less faithful, and the likelihood that vesicles with a cis v-SNARE would fuse with trans-Golgi liposomes increased from 3% to 40%. The group expects that i-SNAREs also work elsewhere, such as at the ER or the plasma membrane, to direct trafficking. ▪