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Weibel-Palade Body Localized Syntaxin-3 Modulates Von Willebrand Factor Secretion From Endothelial Cells.
Schillemans, Maaike; Karampini, Ellie; van den Eshof, Bart L; Gangaev, Anastasia; Hofman, Menno; van Breevoort, Dorothee; Meems, Henriët; Janssen, Hans; Mulder, Aat A; Jost, Carolina R; Escher, Johanna C; Adam, Rüdiger; Carter, Tom; Koster, Abraham J; van den Biggelaar, Maartje; Voorberg, Jan; Bierings, Ruben.
Afiliação
  • Schillemans M; From the Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands (M.S., E.K., B.L.v.d.E., A.G., M.H., D.v.B., H.M., M.v.d.B., J.V., R.B.).
  • Karampini E; From the Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands (M.S., E.K., B.L.v.d.E., A.G., M.H., D.v.B., H.M., M.v.d.B., J.V., R.B.).
  • van den Eshof BL; From the Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands (M.S., E.K., B.L.v.d.E., A.G., M.H., D.v.B., H.M., M.v.d.B., J.V., R.B.).
  • Gangaev A; From the Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands (M.S., E.K., B.L.v.d.E., A.G., M.H., D.v.B., H.M., M.v.d.B., J.V., R.B.).
  • Hofman M; From the Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands (M.S., E.K., B.L.v.d.E., A.G., M.H., D.v.B., H.M., M.v.d.B., J.V., R.B.).
  • van Breevoort D; From the Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands (M.S., E.K., B.L.v.d.E., A.G., M.H., D.v.B., H.M., M.v.d.B., J.V., R.B.).
  • Meems H; From the Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands (M.S., E.K., B.L.v.d.E., A.G., M.H., D.v.B., H.M., M.v.d.B., J.V., R.B.).
  • Janssen H; Cell Biology, The Netherlands Cancer Institute, Amsterdam (H.J.).
  • Mulder AA; Molecular Cell Biology, Section Electron Microscopy, Leiden University Medical Center, The Netherlands (A.A.M., C.R.J., A.J.K.).
  • Jost CR; Molecular Cell Biology, Section Electron Microscopy, Leiden University Medical Center, The Netherlands (A.A.M., C.R.J., A.J.K.).
  • Escher JC; Pediatric Gastroenterology, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands (J.C.E.).
  • Adam R; Pediatric Gastroenterology, University Medical Centre, Mannheim, Germany (R.A.).
  • Carter T; St George's, University of London, United Kingdom (T.C.).
  • Koster AJ; Molecular Cell Biology, Section Electron Microscopy, Leiden University Medical Center, The Netherlands (A.A.M., C.R.J., A.J.K.).
  • van den Biggelaar M; From the Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands (M.S., E.K., B.L.v.d.E., A.G., M.H., D.v.B., H.M., M.v.d.B., J.V., R.B.).
  • Voorberg J; From the Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands (M.S., E.K., B.L.v.d.E., A.G., M.H., D.v.B., H.M., M.v.d.B., J.V., R.B.).
  • Bierings R; Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands (J.V.).
Arterioscler Thromb Vasc Biol ; 38(7): 1549-1561, 2018 07.
Article em En | MEDLINE | ID: mdl-29880488
OBJECTIVE: Endothelial cells store VWF (von Willebrand factor) in rod-shaped secretory organelles, called Weibel-Palade bodies (WPBs). WPB exocytosis is coordinated by a complex network of Rab GTPases, Rab effectors, and SNARE (soluble NSF attachment protein receptor) proteins. We have previously identified STXBP1 as the link between the Rab27A-Slp4-a complex on WPBs and the SNARE proteins syntaxin-2 and -3. In this study, we investigate the function of syntaxin-3 in VWF secretion. APPROACH AND RESULTS: In human umbilical vein endothelial cells and in blood outgrowth endothelial cells (BOECs) from healthy controls, endogenous syntaxin-3 immunolocalized to WPBs. A detailed analysis of BOECs isolated from a patient with variant microvillus inclusion disease, carrying a homozygous mutation in STX3(STX3-/-), showed a loss of syntaxin-3 protein and absence of WPB-associated syntaxin-3 immunoreactivity. Ultrastructural analysis revealed no detectable differences in morphology or prevalence of immature or mature WPBs in control versus STX3-/- BOECs. VWF multimer analysis showed normal patterns in plasma of the microvillus inclusion disease patient, and media from STX3-/- BOECs, together indicating WPB formation and maturation are unaffected by absence of syntaxin-3. However, a defect in basal as well as Ca2+- and cAMP-mediated VWF secretion was found in the STX3-/- BOECs. We also show that syntaxin-3 interacts with the WPB-associated SNARE protein VAMP8 (vesicle-associated membrane protein-8). CONCLUSIONS: Our data reveal syntaxin-3 as a novel WPB-associated SNARE protein that controls WPB exocytosis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator de von Willebrand / Corpos de Weibel-Palade / Células Endoteliais / Proteínas Qa-SNARE / Exocitose / Síndromes de Malabsorção / Microvilosidades / Mucolipidoses Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator de von Willebrand / Corpos de Weibel-Palade / Células Endoteliais / Proteínas Qa-SNARE / Exocitose / Síndromes de Malabsorção / Microvilosidades / Mucolipidoses Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article