Sec22b determines Weibel-Palade body length by controlling anterograde endoplasmic reticulum-Golgi transport

Ellie Karampini, Petra E. Bürgisser, Jenny Olins, Aat A. Mulder, Carolina R. Jost, Dirk Geerts, Jan Voorberg, Ruben Bierings*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)
15 Downloads (Pure)

Abstract

Von Willebrand factor (VWF) is a multimeric hemostatic protein that is synthesized in endothelial cells, where it is stored for secretion in elongated secretory organelles called Weibel-Palade bodies (WPB). The hemostatic activity of VWF is strongly related to the length of these bodies, but how endothelial cells control the dimensions of their WPB is unclear. In this study, using a targeted short hairpin RNA screen, we identified longin-SNARE Sec22b as a novel determinant of WPB size and VWF trafficking. We found that Sec22b depletion resulted in loss of the typically elongated WPB morphology together with disintegration of the Golgi and dilation of rough endoplasmic reticulum cisternae. This was accompanied by reduced proteolytic processing of VWF, accumulation of VWF in the dilated rough endoplasmic reticulum and reduced basal and stimulated VWF secretion. Our data demonstrate that the elongation of WPB, and thus adhesive activity of their cargo VWF, is determined by the rate of anterograde transport between endoplasmic reticulum and Golgi, which depends on Sec22b-containing SNARE complexes.

Original languageEnglish
Pages (from-to)1138-1147
Number of pages10
JournalHaematologica
Volume106
Issue number4
DOIs
Publication statusPublished - Apr 2021

Bibliographical note

Funding Information:
This study was supported by grants from the Landsteiner Stichting voor Bloedtransfusie Research (LSBR-1517 and LSBR-1707), the Netherlands Ministry of Health (PPOC-2015-24P) and the Dutch Thrombosis Foundation (TSN 2017-01).

Publisher Copyright:
© 2021 Ferrata Storti Foundation

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