Sec22b Determines Weibel-Palade Body Length by Controlling Anterograde ER-Golgi Transport

Using electron microscopy the longin-SNARE Sec22b was identified as a novel determinant of WPB size and VWF trafficking.

Sec22b Determines Weibel-Palade Body Length by Controlling Anterograde ER-Golgi Transport

Lead by the group of Ruben Bierings of the Erasmus University Medical Center, we contributed with electron microscopy techniques on the identification of the longin-SNARE Sec22b as a novel determinant of WPB size and VWF trafficking.

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, so-called Weibel-Palade bodies (WPBs). Hemostatic activity of VWF is strongly tied to WPB length, but how endothelial cells control the dimensions of their WPBs is unclear. In this study we used a targeted shRNA screen to identify the 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 along with disintegration of the Golgi and dilation of rough ER (rER) cisternae. This was accompanied by reduced proteolytic processing of VWF, accumulation of VWF in the dilated rER and reduced basal and stimulated VWF secretion. Our data demonstrate that the elongation of WPBs, and thus adhesive activity of its cargo VWF, is determined by the rate of anterograde transport between ER and Golgi, which depends on Sec22b-containing SNARE complexes.

 

Haematologica. 2020 Mar 26;haematol.2019.242727. doi: 10.3324/haematol.2019.242727. Online ahead of print.

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