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

Mol Cell Proteomics. 2009 Feb;8(2):232-44. doi: 10.1074/mcp.M800145-MCP200. Epub 2008 Sep 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Adhesion Molecules / metabolism*
  • Dermis / metabolism
  • Disaccharides / metabolism
  • Epidermis / metabolism*
  • Epitopes
  • Glycomics*
  • Glycopeptides / chemistry
  • Glycoproteins / chemistry
  • Glycoproteins / metabolism*
  • Glycosylation
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Polysaccharides / metabolism
  • Receptors, Cell Surface / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Cell Adhesion Molecules
  • Disaccharides
  • Epitopes
  • Glycopeptides
  • Glycoproteins
  • Polysaccharides
  • Receptors, Cell Surface
  • galactosyl-(1-3)galactose