Syntaxin 5 determines Weibel-Palade body size and von Willebrand factor secretion by controlling Golgi architecture

Marije Kat, Ellie Karampini, Arie J. Hoogendijk, Petra E. Bürgisser, Aat A. Mulder, Floris P.J. Van Alphen, Jenny Olins, Dirk Geerts, Maartje Van den Biggelaar, Coert Margadant, Jan Voorberg, Ruben Bierings*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
32 Downloads (Pure)

Abstract

Von Willebrand factor (VWF) is a multimeric hemostatic protein primarily synthesized in endothelial cells. VWF is stored in endothelial storage organelles, the Weibel-Palade bodies (WPB), 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 endoplasmic reticulum-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 spectrometry-based approach, identifying the Golgi SNARE Syntaxin 5 (STX5). We established STX5 knockdown in endothelial cells using shRNA-dependent silencing and analyzed WPB and Golgi morphology, using confocal and electron microscopy. STX5-depleted endothelial cells 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. In brief, we identified SNARE protein STX5 as a novel regulator of WPB biogenesis.

Original languageEnglish
Pages (from-to)1827-1839
Number of pages13
JournalHaematologica
Volume107
Issue number8
DOIs
Publication statusPublished - 1 Aug 2022

Bibliographical note

Funding Information:
Work in our laboratory was funded by grants from the Landsteiner Stichting voor Bloedtransfusie Research (LSBR-1707) and the Dutch Thrombosis Foundation (TSN 2017-01).

Publisher Copyright:
©2022 Ferrata Storti Foundation.

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