Platelets support extracellular sialylation by supplying the sugar donor substrate

Area of Science:

• Biochemistry
• Hematology
• Cell Biology

Background:

• Circulating glycosyltransferases like ST6Gal-1 are abundant but their function is limited by unidentified sugar donor substrates.
• ST6Gal-1 decorates hematopoietic progenitor cells, influencing blood cell production.
• Platelets release bioactive molecules and have been implicated as a source of glycosylation substrates.

Purpose of the Study:

• To investigate if activated platelets can supply sugar donor substrates for extracellular glycosylation.
• To determine if platelets can provide CMP-sialic acid for ST6Gal-1 activity.

Main Methods:

• A cell-based system was used to test platelet function.
• Thrombin-activated platelets were analyzed for their ability to support ST6Gal-1-mediated sialylation.
• Liquid chromatography-mass spectrometry (LC/MS) was used for structural confirmation of sialylated products.

Main Results:

• Activated platelets effectively substitute for CMP-sialic acid in ST6Gal-1-mediated sialylation.
• Platelets supplied sialic acid to a synthetic acceptor, confirmed by LC/MS.
• The donor substrate, likely CMP-sialic acid, was found in platelet microparticles.

Conclusions:

• Platelets are a viable source of sugar donor substrates for extracellular glycosylation.
• Platelet microparticles may facilitate targeted delivery of glycosylation substrates.
• This discovery advances understanding of glycosylation's role in hematopoiesis and inflammation.