The origin and function of platelet glycosyltransferases
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The origin and function of platelet glycosyltransferases. / Wandall, Hans H; Rumjantseva, Viktoria; Sørensen, Anne Louise Tølbøll; Patel-Hett, Sunita; Josefsson, Emma C; Bennett, Eric P; Italiano, Joseph E; Clausen, Henrik; Hartwig, John H; Hoffmeister, Karin M.
I: Blood, Bind 120, Nr. 3, 19.07.2012, s. 626-635.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - The origin and function of platelet glycosyltransferases
AU - Wandall, Hans H
AU - Rumjantseva, Viktoria
AU - Sørensen, Anne Louise Tølbøll
AU - Patel-Hett, Sunita
AU - Josefsson, Emma C
AU - Bennett, Eric P
AU - Italiano, Joseph E
AU - Clausen, Henrik
AU - Hartwig, John H
AU - Hoffmeister, Karin M
PY - 2012/7/19
Y1 - 2012/7/19
N2 - Platelets are megakaryocyte subfragments that participate in hemostatic and host defense reactions and deliver pro- and anti-angiogenic factors throughout the vascular system. Platelets are anucleated cells and lack a complex secretory apparatus with distinct Golgi/endoplasmic reticulum compartments. However, studies have in the past demonstrated the presence of glycosyltransferase activities associated with platelets. We show that members of three distinct glycosyltransferase families are found within and on the surface of platelets. Immunocytology and flow cytometry results indicate that megakaryocytes package these Golgi-derived glycosyltransferases into vesicles that are sent via proplatelets to nascent platelets, where they accumulate. These glycosyltransferases are active, and intact platelets glycosylate large exogenous substrates. Furthermore, we show that activation of platelets results in release of soluble glycosyltransferase activities and that platelets contain sufficient levels of sugar nucleotides for detection of glycosylation of exogenously added substrates. Blood platelets are therefore a rich source of both glycosyltransferases and donor sugar substrates, which can be released to function in the extracellular space. This platelet glycosylation machinery offers a pathway to a simple glycoengineering strategy improving storage of platelets and may serve hitherto unknown biological functions.
AB - Platelets are megakaryocyte subfragments that participate in hemostatic and host defense reactions and deliver pro- and anti-angiogenic factors throughout the vascular system. Platelets are anucleated cells and lack a complex secretory apparatus with distinct Golgi/endoplasmic reticulum compartments. However, studies have in the past demonstrated the presence of glycosyltransferase activities associated with platelets. We show that members of three distinct glycosyltransferase families are found within and on the surface of platelets. Immunocytology and flow cytometry results indicate that megakaryocytes package these Golgi-derived glycosyltransferases into vesicles that are sent via proplatelets to nascent platelets, where they accumulate. These glycosyltransferases are active, and intact platelets glycosylate large exogenous substrates. Furthermore, we show that activation of platelets results in release of soluble glycosyltransferase activities and that platelets contain sufficient levels of sugar nucleotides for detection of glycosylation of exogenously added substrates. Blood platelets are therefore a rich source of both glycosyltransferases and donor sugar substrates, which can be released to function in the extracellular space. This platelet glycosylation machinery offers a pathway to a simple glycoengineering strategy improving storage of platelets and may serve hitherto unknown biological functions.
U2 - 10.1182/blood-2012-02-409235
DO - 10.1182/blood-2012-02-409235
M3 - Journal article
C2 - 22613794
VL - 120
SP - 626
EP - 635
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -
ID: 38325904