%0 Journal Article
%A Patella, F
%A Cutler, DF
%D 2020
%F discovery:10103547
%J Journal of Cell Science
%K Weibel-Palade bodies; von Willebrand Factor; extracellular matrix; RGS4; constitutive  secretion
%N 14
%T RGS4 controls secretion of von Willebrand factor to the subendothelial matrix
%U https://discovery.ucl.ac.uk/id/eprint/10103547/
%V 133
%X The haemostatic protein von Willebrand Factor (VWF) exists in plasma and subendothelial pools; the  former secreted from endothelial storage granules, Weibel-Palade bodies (WPBs), by basal secretion  with a contribution from agonist-stimulated secretion, the latter secreted into the subendothelial  matrix by a constitutive pathway, not involving WPBs. We set out to determine if the constitutive  release of subendothelial VWF is actually regulated and if so, what functional consequences this might  have.  Constitutive VWF secretion can be increased by a range of factors; changes in VWF expression, levels  of TNF-alpha or other environmental cues. An RNAseq analysis revealed that expression of RGS4  (Regulator of G protein signalling 4) was reduced in endothelial cells (HUVECs) grown under these  conditions. si-RGS4 treatment of HUVECs increased constitutive basolateral secretion of VWF,  probably by affecting the anterograde secretory pathway. In a simple model of endothelial damage  we show that RGS4-silenced cells increased platelet recruitment onto the subendothelial matrix under  flow. These results show that changes in RGS4 expression alter levels of subendothelial VWF, affecting  platelet recruitment. This introduces a novel control over VWF function.
%Z This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.