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Syntaxin 5 determines Weibel-Palade body size and von Willebrand factor secretion by controlling Golgi architecture. / Kat, Marije; Karampini, Ellie; Hoogendijk, Arie J. et al.

In: Haematologica, Vol. 107, No. 8, 01.08.2022, p. 1827-1839.

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Kat M, Karampini E, Hoogendijk AJ, Bürgisser PE, Mulder AA, van Alphen FPJ et al. Syntaxin 5 determines Weibel-Palade body size and von Willebrand factor secretion by controlling Golgi architecture. Haematologica. 2022 Aug 1;107(8):1827-1839. doi: 10.3324/haematol.2021.280121

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@article{01f1a77f703f4ca287f54155dcb39381,
title = "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. 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.",
author = "Marije Kat and Ellie Karampini and Hoogendijk, {Arie J.} and B{\"u}rgisser, {Petra E.} and Mulder, {Aat A.} and {van Alphen}, {Floris P. J.} and Jenny Olins and Dirk Geerts and {van den Biggelaar}, Maartje and Coert Margadant and Jan Voorberg and Ruben Bierings",
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: {\textcopyright}2022 Ferrata Storti Foundation.",
year = "2022",
month = aug,
day = "1",
doi = "10.3324/haematol.2021.280121",
language = "English",
volume = "107",
pages = "1827--1839",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "8",

}

RIS

TY - JOUR

T1 - Syntaxin 5 determines Weibel-Palade body size and von Willebrand factor secretion by controlling Golgi architecture

AU - Kat, Marije

AU - Karampini, Ellie

AU - Hoogendijk, Arie J.

AU - Bürgisser, Petra E.

AU - Mulder, Aat A.

AU - van Alphen, Floris P. J.

AU - Olins, Jenny

AU - Geerts, Dirk

AU - van den Biggelaar, Maartje

AU - Margadant, Coert

AU - Voorberg, Jan

AU - Bierings, Ruben

N1 - 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.

PY - 2022/8/1

Y1 - 2022/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85126069348&partnerID=8YFLogxK

U2 - 10.3324/haematol.2021.280121

DO - 10.3324/haematol.2021.280121

M3 - Article

C2 - 35081689

VL - 107

SP - 1827

EP - 1839

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 8

ER -

ID: 25836549