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Published online 29 December 2003. doi:10.1083/jcb.200307066
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 1, 79-88
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Article

 i-SNAREs : inhibitory SNAREs that fine-tune the specificity of membrane fusion



Oleg Varlamov1, Allen Volchuk1, Vahid Rahimian1, Claudia A. Doege1, Fabienne Paumet1, William S. Eng1, Nancy Arango1, Francesco Parlati1, Mariella Ravazzola2, Lelio Orci2, Thomas H. Söllner1 and James E. Rothman1

1 Department of Cellular Biochemistry and Biophysics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
2 Department of Morphology, University of Geneva Medical School, 1211 Geneva Switzerland

Address correspondence to James E. Rothman, Department of Cellular Biochemistry and Biophysics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 251, New York, NY 10021. Tel.: (212) 639-8598. Fax: (212) 717-3604. email: j-rothman{at}ski.mskcc.org

A new functional class of SNAREs, designated inhibitory SNAREs (i-SNAREs), is described here. An i-SNARE inhibits fusion by substituting for or binding to a subunit of a fusogenic SNAREpin to form a nonfusogenic complex. Golgi-localized SNAREs were tested for i-SNARE activity by adding them as a fifth SNARE together with four other SNAREs that mediate Golgi fusion reactions. A striking pattern emerges in which certain subunits of the cis-Golgi SNAREpin function as i-SNAREs that inhibit fusion mediated by the trans-Golgi SNAREpin, and vice versa. Although the opposing distributions of the cis- and trans-Golgi SNAREs themselves could provide for a countercurrent fusion pattern in the Golgi stack, the gradients involved would be strongly sharpened by the complementary countercurrent distributions of the i-SNAREs.

Key Words: Golgi; vesicles; gradient; homotypic; regulation

F. Parlati's present address is Rigel Pharmaceuticals, Inc., 240 East Grand Avenue, South San Francisco, CA 94080.

Abbreviations used in this paper: CGN, cis-Golgi network; i-SNARE, inhibitory SNARE; tcis, cis-Golgi t-SNARE; ttrans, trans-Golgi t-SNARE; vcis, cis-Golgi v-SNARE; vtrans, trans-Golgi v-SNARE.


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