When was the Last Time You Thought About Glycosylation?

So seriously, when was the last time you thought about glycosylation or how glycosylation might affect your research?
So why are we even asking this question? It turns out that glycosylation, which is the addition of carbohydrates to proteins or other molecules, plays a huge part in protein folding, protein stability, cell adhesion, cellular function and protection, recognition of self, pathogen invasion, and much more. From bacteria to yeast to mammals, it happens everywhere and it happens a lot. Yet in the light of biological research, it is often overlooked or even disregarded. Girl thinking
For example: on embryonic stem cells, many of the defining surface antigens are not proteins, they are sugar structures unique to the stem cells. Antibodies such as TRA-1-60, TRA-1-81, and the SSEA series (1 through 5), all recognize carbohydrate structures. Many other antibodies to CD molecules or other surface molecules are also only specific to the carbohydrate structure rather than the protein itself. Think about this the next time you label cells with an antibody.
Not too surprisingly, due to the abundance of glycans on your cell surfaces, pathogens, such as bacteria and viruses, often target these structures as receptors to enter into cells. The influenza virus, in particular, targets the terminal sialic acid sugars to gain entry into cells.
It is widely understood that cell signaling occurs via phosphorylation of proteins, i.e. phosphorylated kinase proteins go on to phosphorylate other proteins creating a cascading reaction leading to a cellular response. Lots of research dollars (potentially billions) go to study this process and its implications in disease. What is less well known is the carbohydrate modification of O-GlcNAc (O-linked N-acetylglucosamine). This process is ubiquitous among eukaryotes, and happens on a wide variety of intracellular proteins, including nuclear proteins, such as chromatin and RNA polymerase II, as well as cytoskeletal proteins, such as cytokeratins, neurofilaments, and microtubule-associated proteins. Studies indicate that this process is as abundant as phosphorylation and may have opposing effects to phosphorylation, thus bringing balance to signaling, providing an OFF-switch for other ON signals.
The term "phenotype" is commonly used to describe the identifiable antigens on any given cell type. For example, CD4 T helper cells might be phenotyped by anti-CD3 and anti-CD4 antibodies. Similarly "genotype" is used to describe the identifiable sequence of the genes that a person may carry. So why is it that the use of "glycotypes" to identify cells or cellular states, such as activation, differentiation, transformation, etc, not more widely used? Imagine an instrument that can see cancer cells or predict heart attacks or diagnose other diseases based on glycotypes present. Perhaps, the research for this is soon to come.

Perhaps in the future, we will all think about glycosylation a little more often.

You can view the entire Essentials of Glycobiology textbook by A. Varki, et.al. online here.
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