eprintid: 10103547
rev_number: 18
eprint_status: archive
userid: 608
dir: disk0/10/10/35/47
datestamp: 2020-07-07 09:36:34
lastmod: 2021-09-24 22:07:02
status_changed: 2020-07-07 09:36:34
type: article
metadata_visibility: show
creators_name: Patella, F
creators_name: Cutler, DF
title: RGS4 controls secretion of von Willebrand factor to the subendothelial matrix
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D77
keywords: Weibel-Palade bodies; von Willebrand Factor; extracellular matrix; RGS4; constitutive
secretion
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: 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.
date: 2020-07
date_type: published
official_url: https://doi.org/10.1242/jcs.247312
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1794808
doi: 10.1242/jcs.247312
pii: jcs.247312
lyricists_name: Cutler, Daniel
lyricists_id: DFCUT81
actors_name: Cutler, Daniel
actors_id: DFCUT81
actors_role: owner
full_text_status: public
publication: Journal of Cell Science
volume: 133
number: 14
article_number: jcs.247312
event_location: England
citation:        Patella, F;    Cutler, DF;      (2020)    RGS4 controls secretion of von Willebrand factor to the subendothelial matrix.                   Journal of Cell Science , 133  (14)    , Article jcs.247312.  10.1242/jcs.247312 <https://doi.org/10.1242/jcs.247312>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10103547/1/Patella_RGS4_JCS_for%20UCL-OA.pdf