SNAREpins are functionally resistant to disruption by NSF and alphaSNAP.
SNARE (SNAP [soluble NSF (N-ethylmaleimide-sensitive fusion protein) attachment protein] receptor) proteins are required for many fusion processes, and recent studies of isolated SNARE proteins reveal that they are inherently capable of fusing lipid bilayers. Cis-SNARE complexes (formed when vesicle SNAREs [v-SNAREs] and target membrane SNAREs [t-SNAREs] combine in the same membrane) are disrupted by the action of the abundant cytoplasmic ATPase NSF, which is necessary to maintain a supply of uncombined v- and t-SNAREs for fusion in cells. Fusion is mediated by these same SNARE proteins, forming trans-SNARE complexes between membranes. This raises an important question: why doesn't NSF disrupt these SNARE complexes as well, preventing fusion from occurring at all? Here, we report several lines of evidence that demonstrate that SNAREpins (trans-SNARE complexes) are in fact functionally resistant to NSF, and they become so at the moment they form and commit to fusion. This elegant design allows fusion to proceed locally in the face of an overall environment that massively favors SNARE disruption.
Weber
T
T
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Parlati
F
F
McNew
J A
JA
Johnston
R J
RJ
Westermann
B
B
Söllner
T H
TH
Rothman
J E
JE
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D015870:Gene Expression / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D016296:Mutagenesis / Q000502:physiology; D052066:N-Ethylmaleimide-Sensitive Proteins; D017434:Protein Structure, Tertiary; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D051381:Rats; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D013696:Temperature; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; D000255:Adenosine Triphosphate; D052066:N-Ethylmaleimide-Sensitive Proteins; C498733:Nsf protein, mouse; C498737:Nsf protein, rat