Alterations in sialic-acid O-acetylation glycoforms during murine erythrocyte development

Abstract

We used Casd1-deficient mice to confirm that this enzyme is responsible for 9-O-acetylation of sialic acids in vivo. We observed a complete loss of 9-O-acetylation of sialic acid on the surface of myeloid, erythroid and CD4 + T cells in Casd1-deficient mice. Although 9-O-acetylation of sialic acids on multiple hematopoietic lineages was lost, there were no obvious defects in hematopoiesis. Interestingly, erythrocytes from Casd1-deficient mice also lost reactivity to TER-119, a rat monoclonal antibody that is widely used to mark the murine erythroid lineage. The sialic acid glyco-epitope recognized by TER-119 on erythrocytes was sensitive to the sialic acid O-acetyl esterase activity of the hemagglutinin-esterase from bovine coronavirus but not to the corresponding enzyme from the influenza C virus. During erythrocyte development, TER-119 + Ery-A and Ery-B cells could be stained by catalytically inactive bovine coronavirus hemagglutininesterase but not by the inactive influenza C hemagglutinin-esterase, while TER-119 + Ery-C cells and mature erythrocytes were recognized by both virolectins. Although the structure of the sialoglycoconjugate recognized by TER-119 was not chemically demonstrated, its selective binding to virolectins suggests that it may be comprised of a 7,9-di-O-acetyl form of sialic acid. As erythrocytes mature, the surfaces of Ery-C cells and mature erythrocytes also acquire an additional distinct CASD1-dependent 9-O-acetyl sialic acid moiety that can be recognized by virolectins from both influenza C and bovine coronavirus.

Sialic acid O-acetylation: From biosynthesis to roles in health and disease

“…Studying the role of O-Ac-Sias in organisms is challenging, because knock-out of SOATs will broadly remove sialic acid O-acetylation, and remarkably, the recently generated Casd1 knock-out mice are viable and fertile, raising questions concerning the importance of this modification in development (85,86). More specific deletion of the O-Ac-Sia carrier will also only provide limited insight into its role in development.…”

O-acetylated Gangliosides as Targets for Cancer Immunotherapy

“…In these cellular models, CASD1 would not act directly on the GD3 ganglioside, but rather on the activated sialic acid donor, CMP-Neu5Ac [55]. In agreement with a role of CASD1 in sialic acid 9-O-acetylation, CASD1-deficient mice exhibit a complete loss of O-acetylation of Sia on the surface of hematopoietic lineage cells [56]. The biosynthesis pathways for ganglioside O-acetylation remain unclear, especially for species other than OAcGD3, but CASD1 seems to play a key role in the O-acetylation process (Figure 2).…”

Cancer-Associated Glycosphingolipids as Tumor Markers and Targets for Cancer Immunotherapy

“…Data from Baumann and co-workers suggested that CASD1 was involved in 9- O -acetylation of sialic acids in human HAP-1 cells and resulted in increased 9- O AcGD3 expression [ 25 ]. In parallel, CASD1-deficient mice exhibited a complete loss of O -acetylation of sialic acid on the murine erythrocyte cell surface [ 26 ]. Nevertheless, even if CASD1 seems to play a key role in the O -acetylation process, the O -acetylation pathways for gangliosides remain rather unclear, especially for species other than OAcGD3.…”