The extracellular space also has its own class of glycoconjugates. The cell surface and connective matrix of animal tissues are populated by large proteoglycan molecules which have covalently attached glycosaminoglycan chains (GAGs) that may be either N-linked or O-linked to the core protein. GAGs are linear polysaccharides that consist of repeating disaccharide units of hexuronic acid linked to a hexosamine. These large polysaccharides are acidic and/or polyanionic (negatively charged due to numerous sulfate groups). GAG biosynthesis occurs without a template and is largely controlled by enzyme and substrate availabilities, giving rise to a heterogeneous mixture of glycoforms (1). The diverse structural properties of GAGs are important for molecular binding and for tissue morphogenesis (2-4) (Fig. 1). The majority of GAGs are first attached to the core protein and polymerized in the Golgi apparatus, where they are subsequently sulfated following various patterns that greatly affect the biological properties of the molecule. One exception is hyaluronan, which is a non-sulfated free polysaccharide, synthesized at the plasma membrane level (5).
Glycolipids comprise another major class of glycans. These molecules are abundant components of the cellular membrane and consist of a lipid moiety attached to monosaccharide or polysaccharide chains that extend into the extracellular space. There are several classes of glycolipids, including glyceroglycolipids, lipopolysaccharides, glycosphingolipids, and glycosylphosphatidylinositols (6). These molecules have varied functions such as eliciting host immune responses to bacterial infections, modulating cell-cell communication and ensuring proper myelination of axons (7, 8).
One interesting class of glycolipids is the glycosylphosphatidylinositol (GPI) anchor. GPIs are essential molecules that are attached to the carboxy termini of certain proteins and serve to anchor them to the surface of eukaryotic cells. GPI anchored proteins are involved in a diverse array of cellular processes including cell adhesion and signal transduction. Proteins that receive a GPI possess a C-terminal GPI attachment signal peptide that mediates enzymatic addition of a GPI precursor lipid to the protein in the ER. The GPI anchored protein then transits the compartments of the ER and Golgi to the cell surface where it is displayed on the exterior face of the plasma membrane. During this journey, specific enzymes add and subtract components side-branched to the GPI glycan, and remodel the fatty acids of the GPI’s lipid moiety. GPI anchored proteins also typically possess N- and/or O-linked glycans (Fig. 2). GPI anchors seem to have implications in the trafficking and surface localization of a given protein, for instance there seems to be a higher abundance of GPI-anchored proteins in lipid rafts (9).
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