Syntaxin 5 determines Weibel-Palade body size and Von Willebrand factor secretion by controlling Golgi architecture
Syntaxin 5 determines Weibel-Palade body size and Von Willebrand factor secretion by controlling Golgi architecture
Abstract Von Willebrand factor (VWF) is a multimeric hemostatic protein primarily synthesized in endothelial cells (ECs). VWF is stored in endothelial storage organelles, the Weibel-Palade bodies (WPBs), whose biogenesis strongly depends on VWF anterograde trafficking and Golgi architecture. Elongated WPB morphology is correlated to longer VWF strings with better adhesive properties. We previously identified the SNARE SEC22B, which is involved in anterograde ER-to-Golgi transport, as a novel regulator of WPB elongation. To elucidate novel determinants of WPB morphology we explored endothelial SEC22B interaction partners in a mass spectrometrybased approach, identifying the Golgi SNARE Syntaxin 5 (STX5). We established STX5 knockdown in ECs using shRNA-dependent silencing and analyzed WPB and Golgi morphology, using confocal and electron microscopy. STX5-depleted ECs exhibited extensive Golgi fragmentation and decreased WPB length, which was associated with reduced intracellular VWF levels, and impaired stimulated VWF secretion. However, the secretion-incompetent organelles in shSTX5 cells maintained WPB markers such as Angiopoietin 2, P-selectin, Rab27A, and CD63. Taken together, our study has identified SNARE protein STX5 as a novel regulator of WPB biogenesis.
Kat Marije、Mulder Aat A.、Voorberg Jan、Geerts Dirk、Olins Jenny、van den Biggelaar Maartje、Hoogendijk Arie Johan、B¨1rgisser Petra、Bierings Ruben、van Alphen Floris、Karampini Ellie、Margadant Coert
Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of AmsterdamMolecular Cell Biology, Leiden University Medical CenterMolecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam||Experimental Vascular Medicine, Amsterdam University Medical Center, University of AmsterdamMedical Biology, Amsterdam University Medical Center University of AmsterdamMolecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of AmsterdamMolecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of AmsterdamMolecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of AmsterdamHematology, Erasmus University Medical CenterHematology, Erasmus University Medical CenterMolecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of AmsterdamMolecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam||Vascular Biology, Royal College of SurgeonsAngiogenesis laboratory, Cancer Center Amsterdam, Amsterdam University Medical Center
基础医学细胞生物学分子生物学
Kat Marije,Mulder Aat A.,Voorberg Jan,Geerts Dirk,Olins Jenny,van den Biggelaar Maartje,Hoogendijk Arie Johan,B¨1rgisser Petra,Bierings Ruben,van Alphen Floris,Karampini Ellie,Margadant Coert.Syntaxin 5 determines Weibel-Palade body size and Von Willebrand factor secretion by controlling Golgi architecture[EB/OL].(2025-03-28)[2025-05-25].https://www.biorxiv.org/content/10.1101/2021.12.10.472050.点此复制
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