title: The origin and function of platelet glycosyltransferases.
abstract: Platelets are megakaryocyte subfragments that participate in hemostatic and host defense reactions and deliver pro- and antiangiogenic factors throughout the vascular system. Although they are anucleated cells that lack a complex secretory apparatus with distinct Golgi/endoplasmic reticulum compartments, past studies have shown that platelets have glycosyltransferase activities. In the present study, we show that members of 3 distinct glycosyltransferase families are found within and on the surface of platelets. Immunocytology and flow cytometry results indicated 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 the release of soluble glycosyltransferase activities and that platelets contain sufficient levels of sugar nucleotides for detection of glycosylation of exogenously added substrates. Therefore, the results of the present study show that blood platelets are a rich source of both glycosyltransferases and donor sugar substrates that 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 biologic functions.
authors.affiliation: Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen N, Denmark. hhw@sund.ku.dk
authors.forename: Hans H
authors.initials: HH
authors.lastname: Wandall
authors.forename: Viktoria
authors.initials: V
authors.lastname: Rumjantseva
authors.forename: Anne Louise Tølbøll
authors.initials: AL
authors.lastname: Sørensen
authors.forename: Sunita
authors.initials: S
authors.lastname: Patel-Hett
authors.forename: Emma C
authors.initials: EC
authors.lastname: Josefsson
authors.forename: Eric P
authors.initials: EP
authors.lastname: Bennett
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Italiano
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.forename: John H
authors.initials: JH
authors.lastname: Hartwig
authors.forename: Karin M
authors.initials: KM
authors.lastname: Hoffmeister
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism*; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family / Q000502:physiology*; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D053657:Platelet-Rich Plasma / Q000166:cytology; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity / Q000502:physiology; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D005700:Galactosyltransferases; D016695:Glycosyltransferases; D017350:N-Acetylgalactosaminyltransferases; D019158:N-Acetylneuraminic Acid; D012799:Sialyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C118899:Siat7d protein, mouse