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 tissue- or species-specific 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 Galalpha1-3Gal 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 Galalpha1-3Gal epitope. These findings provide mechanistic insight into the causal connection between the genotype and the phenotype seen in alpha3GalT-1-deficient mice and transgenic mice expressing endo-beta-galactosidase C. Because humans do not possess the Galalpha1-3Gal structure on their tissues, we further examined the human dermal and epidermal N-glycome. Comparative glycomics revealed that the GalNAcbeta1-4GlcNAc (N,N'-diacetyllactosediamine) epitope, instead of the Galalpha1-3Gal epitope, was highly expressed in human epidermis.
Uematsu
Rie
R
Graduate School of Advanced Life Science, Hokkaido University, Sapporo, Japan.
Shinohara
Yasuro
Y
Nakagawa
Hiroaki
H
Kurogochi
Masaki
M
Furukawa
Jun-ichi
J
Miura
Yoshiaki
Y
Akiyama
Masashi
M
Shimizu
Hiroshi
H
Nishimura
Shin-ichiro
S
D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D020405:Dermis / Q000378:metabolism; D004187:Disaccharides / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D000939:Epitopes; D054794:Glycomics; D006020:Glycopeptides / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015815:Cell Adhesion Molecules; D004187:Disaccharides; D000939:Epitopes; D006020:Glycopeptides; D006023:Glycoproteins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; C055075:galactosyl-(1-3)galactose