The chemical neurobiology of carbohydrates.

The cell surface displays a complex array of oligosaccharides, glycoproteins, and glycolipids. This diverse mixture of glycans contains a wealth of information, modulating a wide range of processes such as cell migration, proliferation, transcriptional regulation, and differentiation. Glycosylation is one of the most ubiquitous forms of post-translational modification, with more than 50% of the human proteome estimated to be glycosylated. Glycosylation adds another dimension to the complexity of cellular signaling and expands the ability of a cell to modulate protein function. The structural complexity of glycan modifications ranges from the addition of a single monosaccharide unit to polysaccharides containing hundreds of sugars in branched or linear arrays. This chemical diversity enables glycans to impart a vast array of functions, from structural stability and proteolytic protection to protein recognition and modulation of cell signaling networks. Emerging evidence suggests a pivotal role for glycans in regulating nervous system development and function. For instance, glycosylation influences various neuronal processes, such as neurite outgrowth and morphology, and may contribute to the molecular events that underlie learning and memory. Glycosylation is an efficient modulator of cell signaling and has been implicated in memory consolidation pathways. Genetic ablation of glycosylation enzymes often leads to developmental defects and can influence various organismal behaviors such as stress and cognition. Thus, the complexity of glycan functions help to orchestrate * To whom correspondence should be addressed. E-mail: lhw@ its.caltech.edu. Chem. Rev. 2008, 108, 1708–1731 1708