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Involvement of SNAP-23 and syntaxin 6 in human neutrophil exocytosis.

To understand the molecular basis of exocytosis in human neutrophils, the role of syntaxin 6 and SNAP-23 in neutrophil degranulation was examined. Human syntaxin 6 was cloned and identified as a 255-amino acid protein with a carboxy-terminal transmembrane region and two coiled-coil domains. Syntaxin 6 was localized mainly in the plasma membrane of human resting neutrophils, whereas SNAP-23 was located primarily in the mobilizable tertiary and specific granules. SNAP-23 was translocated to the cell surface, colocalizing with syntaxin 6, on neutrophil activation. In vitro binding studies established that SNAP-23 binds to syntaxin 6. Coimmunoprecipitation assays indicated that SNAP-23 interacts with syntaxin 6 in vivo, and this interaction was dramatically increased on neutrophil activation. Antibodies against SNAP-23 inhibited Ca(++) and GTP-gamma-S-induced exocytosis of CD67-enriched specific granules, but they hardly affected exocytosis of the CD63-enriched azurophilic granules, when introduced into electropermeabilized neutrophils. Anti-syntaxin 6 antibodies prevented exocytosis of both CD67- and CD63-enriched granules in electropermeabilized neutrophils. These data show that syntaxin 6 and SNAP-23 are involved in human neutrophil exocytosis, demonstrating that vesicle SNAP receptor-target SNAP receptor (v-SNARE- t-SNARE) interactions modulate neutrophil secretion. Syntaxin 6 acts as a target for secretion of specific and azurophilic granules, whereas SNAP-23 mediates specific granule secretion.

Pubmed ID: 11001914


  • Martín-Martín B
  • Nabokina SM
  • Blasi J
  • Lazo PA
  • Mollinedo F



Publication Data

October 1, 2000

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, CD63
  • Antigens, Neoplasm
  • Calcium
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Cell Degranulation
  • Cell Membrane
  • Cell Membrane Permeability
  • Cloning, Molecular
  • Exocytosis
  • Fluorescent Antibody Technique
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Humans
  • Immunoblotting
  • Membrane Glycoproteins
  • Membrane Proteins
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Neutrophils
  • Platelet Membrane Glycoproteins
  • Qa-SNARE Proteins
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Subcellular Fractions