Glycosylation density in cellular homeostasis

Null mutations in the biosynthetic pathways for the formation of specific branch chains in N- and O-linked glycans result in compensation of epitope density in the remaining chains of the mutant. High-resolution mass spectrometry demonstrates that missing glycan epitopes such as LacNAc and Lewisx moieties in mice with null mutations in specific Golgi enzymes are found on related biosynthetic structures. Similar glycan epitope compensation in mice missing the brain ganglioside GM3 has also been shown. These studies indicate that glycan epitope density on the surface of cells from different tissues is highly regulated. Lectin-glycan signaling interactions are sensitive to glycan density and provide a feedback mechanism for cellular homeostasis.