Phylogenetic-Derived Insights into the Evolution of Sialylation in Eukaryotes: Comprehensive Analysis of Vertebrate β-Galactoside α2,3/6-Sialyltransferases (ST3Gal and ST6Gal)

Abstract

Cell surface of eukaryotic cells is covered with a wide variety of sialylated molecules involved in diverse biological processes and taking part in cell–cell interactions. Although the physiological relevance of these sialylated glycoconjugates in vertebrates begins to be deciphered, the origin and evolution of the genetic machinery implicated in their biosynthetic pathway are poorly understood. Among the variety of actors involved in the sialylation machinery, sialyltransferases are key enzymes for the biosynthesis of sialylated molecules. This review focus on β-galactoside α2,3/6-sialyltransferases belonging to the ST3Gal and ST6Gal families. We propose here an outline of the evolutionary history of these two major ST families. Comparative genomics, molecular phylogeny and structural bioinformatics provided insights into the functional innovations in sialic acid metabolism and enabled to explore how ST-gene function evolved in vertebrates.

Systems glycomics of adult zebrafish identifies organ-specific sialylation and glycosylation patterns

“…About 1–2% of the vertebrate’s genome is believed to be involved in the synthesis and processing of glycans that play roles in most, if not all, biological processes. Of uttermost importance, the sialic acids pathway in higher vertebrates requires a large panel of enzymes with various subcellular localizations including the nuclear cytidine monophosphate (CMP)-5- N -acetyl neuraminic acid (Neu5Ac) synthase (CMAS), the cytosolic UDP- N -acetylglucosamine (GlcNAc) 2-epimerase/N-acetylmannosamine kinase (GNE), the cytosolic cytidine monophosphate-N acetylneuraminic acid hydroxylase (CMAH), the Golgi CMP-Neu5Ac transporter (SLC35A1), the Golgi sialyltransferases (ST), and sialidases (Neu) 15 . Thus, it comes as no surprise that any deregulation of glycan synthesis, trafficking, turn-over, or localization may induce variable clinical effects.…”

ST3GAL3, ST3GAL4, and ST3GAL6 differ in their regulation of biological functions via the specificities for the α2,3‐sialylation of target proteins

“…2,3 β-Galactoside α2,3-sialyltransferase1 (ST3GAL1) and ST3GAL2-6 and β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) and ST6GAL2 in the Golgi apparatus are responsible for the syntheses of Neu5Ac(α2,3)Gal and Neu5Ac(α2,6)Gal. [8][9][10] There is ample evidence that sialic acids are important bioinformatic molecules, which play pivotal roles in biological, pathological, and immunological processes through modifying glycoproteins and glycolipids on the cell surface, including nervous system embryogenesis, 11 cell-cell interactions, 12,13 signal transduction, 14 bacterial and viral infection, 15,16 etc In addition, sialic acids on cell membranes are closely related to tumor invasion and metastasis. 5 ST3GAL5 is almost exclusively used in lactosyl-ceramide as an acceptor substrate for GM3 production, which is also known as GM3-synthase.…”

“…7 On the other hand, ST6GAL1 appears to play an important role in the synthesis of N-glycans terminated with Neu5Ac(α2,6)Gal in many kinds of cells and tissues. [8][9][10] There is ample evidence that sialic acids are important bioinformatic molecules, which play pivotal roles in biological, pathological, and immunological processes through modifying glycoproteins and glycolipids on the cell surface, including nervous system embryogenesis, 11 cell-cell interactions, 12,13 signal transduction, 14 bacterial and viral infection, 15,16 etc In addition, sialic acids on cell membranes are closely related to tumor invasion and metastasis. 17,18 Many studies have shown that the expression of ST6GAL1 is increased in diverse carcinomas, which may highly correlate with tumor progression.…”

Probing the CMP‐Sialic Acid Donor Specificity of Two Human β‐d‐Galactoside Sialyltransferases (ST3Gal I and ST6Gal I) Selectively Acting on O‐ and N‐Glycosylproteins

“…It is interesting to note that the evolutionarily related mammalian polysialyltransferases ST8Sia II and ST8Sia IV differentially use N‐acyl derivatives of Neu5Ac, thus suggesting diverse donor substrate affinities . In order to address this question, we focused on the most widely known human glycoprotein β‐ d ‐galactoside α2,3/6‐sialyltransferases: ST6Gal I and ST3Gal I . These two enzymes catalyze the formation of α‐2–6 or α‐2–3 glycosidic linkages on the terminal Gal of type‐II (Galβ1,4Glc N Ac) and type‐III (Galβ1,3Gal N Ac) disaccharides found on N‐glycans and O‐glycans, respectively.…”