title: Effect of dominant negative SNAP-23 expression on platelet function.
abstract: BACKGROUND
  The protein SNAP-23 is part of the secretory pathway in platelets. It is, however, not entirely clear to what extent this protein contributes to the secretory function of platelets. Therefore, we overexpressed a dominant negative mutant with a novel technology that allows the creation of intact transgene-expressing platetets.
  
  
  RESULTS
  Overexpression of a dominant negative SNAP-23 mutant that inhibited the binding of the native protein to the docking site within the secretory machinery resulted in significant suppression of the agonist-dependent surface recruitment of P-selectin and CD40L. Simultaneously, release from dense granules was clearly suppressed in the presence of this construct. Also agonist-dependent surface expression of fibrinogen receptor markers CD41 and CD61 was reduced, and agonist-triggered aggregation was inhibited.
  
  
  CONCLUSIONS
  The dominant negative inhibition of SNAP-23 resulted in clear effects on platelet functions. The novel method using recombinant culture-derived platelets allowed the rapid clarification of the functional importance of this protein in intact platelets.
authors.affiliation: Trigen AG, Martinsried, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Gillitzer
authors.forename: M
authors.initials: M
authors.lastname: Peluso
authors.forename: A
authors.initials: A
authors.lastname: Bültmann
authors.forename: G
authors.initials: G
authors.lastname: Münch
authors.forename: M
authors.initials: M
authors.lastname: Gawaz
authors.forename: M
authors.initials: M
authors.lastname: Ungerer
mesh_terms: D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D023201:CD40 Ligand; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D039661:Integrin beta3; D050505:Mutant Proteins; D019007:P-Selectin; D010974:Platelet Aggregation; D040201:Platelet Membrane Glycoprotein IIb; D050766:Qb-SNARE Proteins / Q000235:genetics* / Q000502:physiology; D050767:Qc-SNARE Proteins / Q000235:genetics* / Q000502:physiology; D055571:Secretory Pathway; D014162:Transfection
chemical_list: D039661:Integrin beta3; D050505:Mutant Proteins; D019007:P-Selectin; D040201:Platelet Membrane Glycoprotein IIb; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C100493:SNAP23 protein, human; D023201:CD40 Ligand