A critical role for N-ethylmaleimide-sensitive fusion protein (NSF) in platelet granule secretion

János Polgár, Guy Reed

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The molecular mechanisms that regulate membrane targeting/fusion during platelet granule secretion are not yet understood. N-ethylmaleimide-sensitive fusion protein (NSF), soluble NSF attachment proteins (SNAPs), and SNAREs (SNAP receptors) are elements of a conserved molecular machinery for membrane targeting/fusion that have been detected in platelets. We examined whether NSF, an ATPase that has been shown to play a critical role in membrane targeting/fusion in many cell types, is necessary for platelet granule secretion. Peptides that mimic NSF sequence motifs inhibited both α-granule and dense-granule secretion in permeabilized human platelets. This inhibitory effect was sequence-specific, because neither proteinase K-digested peptides nor peptides containing similar amino acids in a scrambled sequence inhibited platelet secretion. The peptides that inhibited platelet granule secretion also inhibited the human recombinant α-SNAP-stimulated ATPase activity of recombinant NSF. It was also found that anti-NSF antibodies, which inhibited recombinant α-SNAP-stimulated ATPase activity of NSF, inhibited platelet granule secretion in permeabilized cells. The inhibition by anti-NSF antibodies was abolished by the addition of recombinant NSF. These data provide the first functional evidence that NSF plays an important role in platelet granule secretion.

Original languageEnglish (US)
Pages (from-to)1313-1318
Number of pages6
JournalBlood
Volume94
Issue number4
StatePublished - Aug 15 1999

Fingerprint

N-Ethylmaleimide-Sensitive Proteins
Platelets
Blood Platelets
Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
Membrane Fusion
Adenosine Triphosphatases
Peptides
Fusion reactions
Membranes
SNARE Proteins
Endopeptidase K
Amino Acid Motifs
Antibodies
Machinery

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

A critical role for N-ethylmaleimide-sensitive fusion protein (NSF) in platelet granule secretion. / Polgár, János; Reed, Guy.

In: Blood, Vol. 94, No. 4, 15.08.1999, p. 1313-1318.

Research output: Contribution to journalArticle

Polgár, János ; Reed, Guy. / A critical role for N-ethylmaleimide-sensitive fusion protein (NSF) in platelet granule secretion. In: Blood. 1999 ; Vol. 94, No. 4. pp. 1313-1318.
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