Type

Journal Article

Authors

James S O'Donnell
Roger J S Preston
Jan Voorberg
Richard O'Kennedy
Orla Rawley
Jamie M O'Sullivan
Barry Byrne
Maartje van den Biggelaar
Rachel T McGrath

Subjects

Biochemistry

Topics
blood platelets blood coagulation biosynthesis von willebrand factor glycosylation cytology abo blood group system physiology humans gene expression regulation secretory vesicles proteolysis adamts13 protein human adam proteins chemistry genetics platelet activation metabolism hek293 cells

Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis. (2013)

Abstract Platelet-von Willebrand factor (VWF) is stored within α-granules and accounts for ∼20% of total VWF in platelet-rich plasma. This platelet-VWF pool is distinct from plasma-VWF and is enriched in high molecular weight multimers (HMWM). Previous studies have described significant functional discrepancies between platelet-VWF and plasma-VWF; however, the molecular basis of these differences is not well understood. We have characterized terminal glycan expression on platelet-VWF. Our findings demonstrate that platelet-VWF exists as a distinct natural glycoform. In particular, N-linked sialylation is markedly reduced (>50%) compared with plasma-VWF. Moreover, unlike plasma-VWF, platelet-VWF does not express AB blood group determinants, although precursor H antigen expression is similar to that on plasma-VWF. Because of this differential glycosylation, platelet-VWF exhibits specific resistance to ADAMTS13 proteolysis. Thus platelet activation at sites of vascular injury results in the release of high local concentrations of HMWM platelet-VWF that is more resistant to ADAMTS13, thereby facilitating platelet-plug formation.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

James S O'Donnell, Roger J S Preston, Jan Voorberg, Richard O'Kennedy, Orla Rawley, Jamie M O'Sullivan, Barry Byrne, Maartje van den Biggelaar, Rachel T McGrath

Experts in our system

1
James S O'Donnell
Trinity College Dublin
Total Publications: 57
 
2
Roger J S Preston
Trinity College Dublin
Total Publications: 32
 
3
R O'Kennedy
Dublin City University
Total Publications: 197
 
4
Orla Rawley
Trinity College Dublin
Total Publications: 6
 
5
Jamie M O'Sullivan
Royal College of Surgeons in Ireland
Total Publications: 12
 
6
Barry Byrne
Dublin City University
Total Publications: 15