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

Shaojing Ye, Zubair A. Karim, Rania Al Hawas, Jeffery E. Pessin, Alexandra H. Filipovich, Sidney W. Whiteheart

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

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. SemiquantitativeWestern 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.

Original languageEnglish (US)
Pages (from-to)2484-2492
Number of pages9
JournalBlood
Volume120
Issue number12
DOIs
StatePublished - Sep 20 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet secretion'. Together they form a unique fingerprint.

  • Cite this

    Ye, S., Karim, Z. A., Al Hawas, R., Pessin, J. E., Filipovich, A. H., & Whiteheart, S. W. (2012). Syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet secretion. Blood, 120(12), 2484-2492. https://doi.org/10.1182/blood-2012-05-430603