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

doi:10.1083/jcb.200307066

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 bysubstituting for or binding to a subunit of a fusogenic SNAREpinto form a nonfusogenic complex. Golgi-localized SNAREs weretested for i-SNARE activity by adding them as a fifth SNAREtogether with four other SNAREs that mediate Golgi fusion reactions.A striking pattern emerges in which certain subunits of thecis-Golgi SNAREpin function as i-SNAREs that inhibit fusionmediated by the trans-Golgi SNAREpin, and vice versa. Althoughthe opposing distributions of the cis- and trans-Golgi SNAREsthemselves could provide for a countercurrent fusion patternin the Golgi stack, the gradients involved would be stronglysharpened by the complementary countercurrent distributionsof 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; t_cis, cis-Golgi t-SNARE; t_trans, trans-Golgit-SNARE; v_cis, cis-Golgi v-SNARE; v_trans, trans-Golgi v-SNARE.

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