title: i-SNAREs: inhibitory SNAREs that fine-tune the specificity of membrane fusion.
abstract: 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.
authors.affiliation: Department of Cellular Biochemistry and Biophysics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 251, New York, NY 10021, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Varlamov
authors.forename: Allen
authors.initials: A
authors.lastname: Volchuk
authors.forename: Vahid
authors.initials: V
authors.lastname: Rahimian
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Doege
authors.forename: Fabienne
authors.initials: F
authors.lastname: Paumet
authors.forename: William S
authors.initials: WS
authors.lastname: Eng
authors.forename: Nancy
authors.initials: N
authors.lastname: Arango
authors.forename: Francesco
authors.initials: F
authors.lastname: Parlati
authors.forename: Mariella
authors.initials: M
authors.lastname: Ravazzola
authors.forename: Lelio
authors.initials: L
authors.lastname: Orci
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Söllner
authors.forename: James E
authors.initials: JE
authors.lastname: Rothman
mesh_terms: D001665:Binding Sites / Q000502:physiology; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D050600:SNARE Proteins; D015398:Signal Transduction / Q000502:physiology; D033921:Vesicular Transport Proteins; D021601:trans-Golgi Network / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D021122:Protein Subunits; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins