The hemagglutinin (HA) proteins on the influenza virus membrane recognize Sia residues on host cell surface glycoconjugates

The hemagglutinin (HA) proteins on the influenza virus membrane recognize Sia residues on host cell surface glycoconjugates. viral hemagglutinins, Siglecs and selectins. In the second half of this section, we comment on the role of sialylated N-glycans in cancer, including the roles of Mouse monoclonal to FLT4 1-integrin and Fas receptor N-glycan sialylation in cancer cell survival and drug resistance, and the role of these sialylated proteins and polysialic acid in cancer metastasis. with forward by Gabius (2015) for a broad overview of all forms glycosylation and their function. Finally, there are numerous excellent reviews referenced throughout the text on all aspects of N-glycan sialylation that we encourage the reader to consider. We also want to sincerely apologize to the authors of many fine papers that we did not have the room to include. Apigenin-7-O-beta-D-glucopyranoside Sialyltransferases: structure and function This discussion will focus on the STs involved in the modification of N-glycans in mammalian cells including the ST6Gal-I and ST6Gal-II, ST3Gal-IV and ST3Gal-VI, and the polysialyltransferases (polySTs), ST8Sia-II and ST8Sia-IV (see Fig.?1 for the structures formed by these STs on N-glycans). We will discuss these enzymes substrates and general function, their common domain structure and conserved sequences, the molecular structure of the ST6Gal-I, the ST catalytic mechanism and mechanism underlying the protein specificity of polysialylation. Open in a separate window Fig.?1 N-glycan structures synthesized by 2,3-, 2,6- and 2,8-sialyltransferases. In this review, we have focused on the sialyltransferases that add Sia to N-glycans. The ST3Gal enzymes may also modify O-glycans and glycolipids, while the role of ST6Gal-II in modifying protein-bound N-glycans has not been unequivocally demonstrated. The polysialyltransferases, ST8Sia-II and ST8Sia-IV, synthesize polySia chains of 8 to greater than 400 units long on a preexisting Sia that is many times 2,6-linked. Shown is a triantennary N-glycan as a model and does not imply that the activity of these enzymes in any way is restricted to this type of N-glycan. Pink diamond, Neu5Ac; edited by J. Roth, U. Rutishauser and F. A. Troy II (Roth et al. 1993). In mammals, polySia is found on N- and O-linked glycans and is essential for cell migration and plasticity during nervous system development and to maintain these processes in select areas of the adult brain such as the hippocampus, olfactory bulb and hypothalamus [reviewed in Colley et al. (2014), Rutishauser (2008), Schnaar et al. (2014)]. More Apigenin-7-O-beta-D-glucopyranoside recent work has demonstrated a role for polySia in regeneration of damaged neurons (El Maarouf et al. 2006; El Maarouf and Rutishauser 2010; Zhang et al. 2007a, b), and in liver development Apigenin-7-O-beta-D-glucopyranoside and regeneration (Tsuchiya et al. 2014). In addition, many cancer cells upregulate polySia, and its expression correlates with increased invasion and metastasis (Colley et al. 2014; Falconer et al. 2012). For sometime, polySia was believed to exert its effects exclusively through an anti-adhesive mechanism; however, more recently, its ability to impact signaling, either directly by controlling proteinCprotein interactions or indirectly by serving as a reservoir for signaling molecules, has been appreciated (Colley et al. 2014; Schnaar et al. 2014). Interestingly, polySia is also being used as a less immunogenic and more biodegradable substitute for polyethylene glycol (PEG) to enhance the stability and circulating half-life of therapeutic proteins [reviewed in Bader and Wardwell (2014), Colley et al. (2014)], and as part of nanoparticles for drug delivery (Zhang et al. 2014, 2016). Apigenin-7-O-beta-D-glucopyranoside Please see below for a discussion of the protein specificity of polysialylation, its role cancer, and the article in this issue by Higuero and colleagues that discusses the role of glycans, including polySia, in CNS and PNS development.