Clinical impact of glycans in platelet and megakaryocyte biology

Abstract

Humans produce and remove 1011 platelets daily to maintain a steady-state platelet count. The production of platelets by bone marrow megakaryocytes and their removal from the blood circulation are tightly regulated mechanisms, and abnormalities in both processes can result in thrombocytopenia (low platelet count) or thrombocytosis (high platelet count), often associated with the risk of bleeding or overt thrombus formation, respectively. This review focuses on the role of glycans, also known as carbohydrates or oligosaccharides, including N- and O-glycans, proteoglycans, and glycosaminoglycans, in human and mouse platelet and megakaryocyte physiology. Based on recent clinical observations and mouse models, we focused on the pathological aspects of glycan biosynthesis and degradation and its effects on platelet numbers and megakaryocyte function.

Analysis of the Healthy Platelet Proteome Identifies a New Form of Domain-Specific O-Fucosylation

“…O- Glycosylation is known to play an important regulatory role in cellular function; however, the majority of platelet studies have focused on the role of N-glycans and O- sialic acids in platelet production and clearance ( 68 , 69 ). Importantly, defective O- glycosylation of platelet proteins results in a bleeding phenotype ( 70 ).…”

Ultra-sensitive platelet proteome maps the O-glycosylation landscape and charts the response to thrombin dosage

“…O-glycosylation is known to play an important regulatory role in cellular function, however, the majority of platelet studies have focused on the role of N-glycans and O-sialic acids in platelet production and clearance 48,49 . Defective O-glycosylation of platelet proteins results in a bleeding phenotype 50 .…”

Inside-to-outside and back to the future of megakaryopoiesis

“…Knowledge about the expression and role of GAGs in the bone marrow and their relevance for the regulation of megakaryocyte functions is rapidly growing, as recently reviewed by Falet et al. [ 27 ] Several studies reported that heparin, heparan sulfate, dermatan sulfate, chondroitin sulfate, and hyaluronic acid stimulate megakaryopoiesis [ 27 ]. Perlecan, a heparan sulfate proteoglycan, is abundantly expressed in the bone marrow, where it regulates megakaryocyte maturation and guides proplatelet formation in the lumen of sinusoidal blood vessels through binding to the G6b-B receptor [ 28 ].…”