Down Regulation of the Munc18b-syntaxin-11 Complex and β1-tubulin Impairs Secretion and Spreading in Neonatal Platelets

Thromb Haemost. 2017 Nov;117(11):2079-2091. doi: 10.1160/TH17-04-0241. Epub 2017 Nov 30.


Neonatal platelets are hyporeactive and show impaired agonist-induced secretion despite no obvious abnormalities in their granules. Here, we examined, for the first time, the ultrastructure of neonatal and adult platelets following agonist activation. Under resting conditions, neonatal and adult platelets appeared ultrastructurally identical. Following agonist stimulation, however, noticeable degranulation occurred in adult platelets, while granules in neonatal platelets remained clearly visible and apparently unable to centralize or fuse. To investigate the underlying mechanisms, we first examined the expression levels of the main SNARE proteins, which mediate the membrane fusion events required for exocytosis. Neonatal platelets showed significantly reduced levels of syntaxin-11 and its regulator, Munc18b. Since granule centralization depends on contraction of the microtubule ring, we also examined the expression of its main component, β1-tubulin. Noteworthy, we found decreased TUBB1 mRNA and protein levels in neonatal platelets, while TUBB2A and TUBB isoforms were overexpressed, partially compensating for that deficiency. Finally, supporting the functional consequences of defective exocytosis, adhesion kinetic assays, performed in plasma-free medium, demonstrated delayed adhesion and spreading of neonatal platelets. This is the first report showing marked reductions of syntaxin-11-Munc18b complex and β1-tubulin in neonatal platelets, indicating that these proteins, required for platelet degranulation, are developmentally regulated.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Age Factors
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Blood Platelets / ultrastructure
  • Cell Degranulation* / drug effects
  • Cell Shape* / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Exocytosis* / drug effects
  • Fetal Blood / cytology
  • Humans
  • Infant, Newborn
  • Kinetics
  • Multiprotein Complexes
  • Munc18 Proteins / genetics
  • Munc18 Proteins / metabolism*
  • Peptide Fragments / pharmacology
  • Platelet Adhesiveness
  • Qa-SNARE Proteins / genetics
  • Qa-SNARE Proteins / metabolism*
  • Signal Transduction
  • Tubulin / genetics
  • Tubulin / metabolism*


  • Multiprotein Complexes
  • Munc18 Proteins
  • Peptide Fragments
  • Qa-SNARE Proteins
  • STX11 protein, human
  • STXBP2 protein, human
  • TUBB1 protein, human
  • Tubulin
  • thrombin receptor peptide SFLLRNP