Bitter sweetness of complexity.

Glycosylation of proteins, lipids and mucins has gained increasing complexity in the course of evolution. Metazoans and mammals exhibit extensively exploited pathways of N-glycan biosynthesis, with unique features that are not found in plants or protozoans.Paralleling the complexity of N-glycan structure, their impact on regulatory processes has become very diverse and has evolved into a multidimensional lattice imprinting modes of cellular communication. Processes that are regulated by N-glycans are cellular adhesion and motility, growth factor and cytokine signalling, metabolic homeostasis, and binding of certain pathogens. Consequently, alterations in N-glycan biosynthesis interfere with cellular proliferation and differentiation and may produce disturbances in embryonic development, trigger inflammatory processes, favour tumour development and enhance the metastastic dissemination of primary tumours. Particular N-glycans that have been causally related to these pathological scenarios are the complex-type N-glycans, branching from oligomannosidic core structures into β-glycosidic linkages, connected to acetylated glucosamine and galactose, and yield extended lactosamine chains of variable length. These N-acetyllactosamines are preferred building blocks for further modification by fucosylation, sialylation, and sulphation, thus creating binding sites for different galectins or selectins. The focus of this review will be on the b1,6-N -acetylglucosaminyltransferase-V/GnT-V/MGAT5, a phylogenically conserved enzyme that is required for the synthesis of β1,6-branched complex-type oligosaccharides in the medial Golgi compartment, and its implications in metabolism and cancer progression.