Glycosylation specific for adhesion molecules in epidermis and its receptor revealed by glycoform-focused reverse genomics.

Glycosylation of proteins greatly affects their structure and function, but traditional genomics and transcriptomics are not able to precisely capture tissueor speciesspecific glycosylation patterns. We describe here a novel approach to link different “omics” data based on exhaustive quantitative glycomics of murine dermis and epidermis. We first examined the dermal and epidermal N-glycome of mouse by a recently established glycoblotting technique. We found that the Gal 1–3Gal epitope was solely expressed in epidermis tissue and was preferentially attached to adhesion molecules in a glycosylation site-specific manner. Clarified glycomic and protemic information combined with publicly available microarray data sets allowed us to identify galectin-3 as a receptor of Gal 1–3Gal epitope. These findings provide mechanistic insight into the causal connection between the genotype and the phenotype seen in 3GalT-1-deficient mice and transgenic mice expressing endo-galactosidase C. Because humans do not possess the Gal 1–3Gal structure on their tissues, we further examined the human dermal and epidermal N-glycome. Comparative glycomics revealed that the GalNAc 1–4GlcNAc (N,N -diacetyllactosediamine) epitope, instead of the Gal 1–3Gal epitope, was highly expressed in human epidermis. Molecular & Cellular Proteomics 8:232–244, 2009.