i-SNAREs: inhibitory SNAREs that fine-tune the specificity of membrane fusion.
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.
Varlamov
Oleg
O
Department of Cellular Biochemistry and Biophysics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 251, New York, NY 10021, USA.
Volchuk
Allen
A
Rahimian
Vahid
V
Doege
Claudia A
CA
Paumet
Fabienne
F
Eng
William S
WS
Arango
Nancy
N
Parlati
Francesco
F
Ravazzola
Mariella
M
Orci
Lelio
L
Söllner
Thomas H
TH
Rothman
James E
JE
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
D008565:Membrane Proteins; D021122:Protein Subunits; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins