Putative fusogenic activity of NSF is restricted to a lipid mixture whose coalescence is also triggered by other factors Journal Article

Authors: Brügger, B.; Nickel, W.; Weber, T.; Parlati, F.; Mcnew, J. A.; Rothman, J. E.; Söllner, T.
Article Title: Putative fusogenic activity of NSF is restricted to a lipid mixture whose coalescence is also triggered by other factors
Abstract: It has recently been reported that N-ethylmaleimide-sensitive fusion ATPase (NSF) can fuse protein-free liposomes containing substantial amounts of 1,2-dioleoyl-phosphatidylserine (DOPS) and 1,2-dioleoyl-phosphatidyl-ethanolamine (DOPE). The authors impart physiological significance to this observation and propose to re-conceptualize the general role of NSF in fusion processes. We can confirm that isolated NSF can fuse liposomes of the specified composition. However, this activity of NSF is resistant to inactivation by N-ethylmaleimide and does not depend on the presence of α-SNAP (soluble NSF-attachment protein). Moreover, under the same conditions, either α-SNAP, other proteins apparently unrelated to vesicular transport (glyceraldehyde-3-phosphate dehydrogenase or lactic dehydrogenase) or even 3 mM magnesium ions can also cause lipid mixing. In contrast, neither NSF nor the other proteins nor magnesium had any significant fusogenic activity with liposomes composed of a biologically occurring mixture of lipids. A straightforward explanation is that the lipid composition chosen as optimal for NSF favors non-specific fusion because it is physically unstable when formed into liposomes. A variety of minor perturbations could then trigger coalescence.
Keywords: animals; lipid; membrane proteins; enzyme activity; carrier proteins; membrane protein; thermodynamics; lactate dehydrogenase; rats; glyceraldehyde 3 phosphate dehydrogenase; adenosine triphosphate; phosphatidylethanolamines; adenosine triphosphatase; lipid metabolism; adenosine triphosphatases; l-lactate dehydrogenase; liposome; liposomes; fusion; magnesium ion; magnesium; lipid composition; vesicular transport proteins; membrane fusion; vesicle; golgi apparatus; phosphatidylcholines; snare proteins; snare; phosphatidylserines; priority journal; article; nsf; n-ethylmaleimide-sensitive proteins; soluble n-ethylmaleimide-sensitive factor attachment proteins; n ethylmaleimide; glyceraldehyde-3-phosphate dehydrogenases; ethylmaleimide
Journal Title: EMBO Journal
Volume: 19
Issue: 6
ISSN: 0261-4189
Publisher: Wiley Blackwell  
Date Published: 2000-03-15
Start Page: 1272
End Page: 1278
Language: English
PUBMED: 10716927
PROVIDER: scopus
PMCID: PMC305668
DOI: 10.1093/emboj/19.6.1272
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Thomas H Sollner
    65 Sollner
  2. James E Rothman
    102 Rothman
  3. Thomas Weber
    14 Weber
  4. James A Mcnew
    21 McNew
  5. Francesco Parlati
    17 Parlati
  6. Hans-Walter Karl Nickel
    8 Nickel