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Syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet secretion.

The platelet release reaction plays a critical role in thrombosis and contributes to the events that follow hemostasis. Previous studies have shown that platelet secretion is mediated by Soluble NSF Attachment Protein Receptor (SNARE) proteins from granule and plasma membranes. The SNAREs form transmembrane complexes that mediate membrane fusion and granule cargo release. Although VAMP-8 (v-SNARE) and SNAP-23 (a t-SNARE class) are important for platelet secretion, the identity of the functional syntaxin (another t-SNARE class) has been controversial. Previous studies using anti-syntaxin Abs in permeabilized platelets have suggested roles for both syntaxin-2 and syntaxin-4. In the present study, we tested these conclusions using platelets from syntaxin-knockout mouse strains and from a Familial Hemophagocytic Lymphohistiocytosis type 4 (FHL4) patient. Platelets from syntaxin-2 and syntaxin-4 single- or double-knockout mice had no secretion defect. Platelets from a FHL4 patient deficient in syntaxin-11 had a robust defect in agonist-induced secretion although their morphology, activation, and cargo levels appeared normal. Semiquantitative Western blotting showed that syntaxin-11 is the more abundant syntaxin in both human and murine platelets. Coimmunoprecipitation experiments showed that syntaxin-11 can form SNARE complexes with both VAMP-8 and SNAP-23. The results of the present study indicate that syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet exocytosis.

Pubmed ID: 22767500


  • Ye S
  • Karim ZA
  • Al Hawas R
  • Pessin JE
  • Filipovich AH
  • Whiteheart SW



Publication Data

September 20, 2012

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI076746
  • Agency: NIAID NIH HHS, Id: AI079759
  • Agency: NHLBI NIH HHS, Id: HL082193
  • Agency: NHLBI NIH HHS, Id: HL56652
  • Agency: NCRR NIH HHS, Id: P20 RR020171
  • Agency: NHLBI NIH HHS, Id: R01 HL056652
  • Agency: NCRR NIH HHS, Id: S10 RR026827

Mesh Terms

  • Animals
  • Blood Platelets
  • Cell Membrane
  • Cytoplasmic Granules
  • Exocytosis
  • Female
  • Humans
  • Immunoprecipitation
  • Lymphohistiocytosis, Hemophagocytic
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Aggregation
  • Qa-SNARE Proteins
  • Syntaxin 1