Extrinsic sialylation is dynamically regulated by systemic triggers in vivo

Area of Science:

• Biochemistry
• Glycobiology
• Cell Biology

Background:

• Extracellular sialyltransferases can modify cell-surface and secreted glycans through a non-canonical pathway.
• The in vivo prevalence of this extrinsic glycosylation pathway, particularly involving ST6Gal-1, is largely unknown despite its association with diseases like cancer and inflammation.

Purpose of the Study:

• To investigate the in vivo occurrence and triggers of extrinsic sialylation.
• To determine the role of circulating components, such as platelets, in extrinsic glycosylation.
• To explore the specific sialyltransferases involved in this pathway.

Main Methods:

• Assessment of extrinsic sialylation in resting and challenged mice (ionizing radiation, lipopolysaccharides).
• Utilized FeCl₃-induced thrombosis model to study platelet activation and extrinsic sialylation.
• Investigated extrinsic sialylation in ST6Gal-1 deficient mice.

Main Results:

• Extrinsic sialylation was not observed in resting mice, indicating it's not a constitutive process.
• Inflammatory challenges and platelet activation significantly triggered extrinsic sialylation in vivo.
• Circulating platelets serve as a source of sialic acids for target cell remodeling, and extrinsic sialylation is not exclusively mediated by ST6Gal-1.

Conclusions:

• Extrinsic sialylation is an inducible process in vivo, primarily activated by inflammatory conditions and platelet activation.
• This pathway involves remodeling of glycans synthesized via the canonical pathway by extracellular glycan-modifying enzymes.
• Platelets play a crucial role in supplying sialic acids for extrinsic glycosylation, expanding our understanding of glycan regulation in vivo.