O-linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell-matrix interactions

Nat Commun. 2011 Dec 13;2:583. doi: 10.1038/ncomms1591.

Abstract

The O-linked-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates basic cellular functions and is involved in the aetiology of diabetes and neurodegeneration. This intracellular O-GlcNAcylation is catalyzed by a single O-GlcNAc transferase, OGT. Here we report a novel OGT, EOGT, responsible for extracellular O-GlcNAcylation. Although both OGT and EOGT are regulated by hexosamine flux, EOGT localizes to the lumen of the endoplasmic reticulum and transfers GlcNAc to epidermal growth factor-like domains in an OGT-independent manner. Loss of Eogt gives phenotypes similar to those caused by defects in the apical extracellular matrix. Dumpy (Dp), a membrane-anchored extracellular protein, is O-GlcNAcylated, and EOGT is required for Dp-dependent epithelial cell-matrix interactions. Thus, O-GlcNAcylation of secreted and membrane glycoproteins is a novel mediator of cell-cell or cell-matrix interactions at the cell surface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Acylation
  • Amino Acid Sequence
  • Animals
  • Cell Communication / genetics*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics*
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Hexosamines / metabolism
  • Mice
  • Molecular Sequence Data
  • N-Acetylglucosaminyltransferases / chemistry
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism*
  • Plasmids
  • Protein Binding
  • Protein Processing, Post-Translational / genetics
  • Protein Structure, Tertiary
  • RNA Interference
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Transfection

Substances

  • DPY protein, Drosophila
  • Drosophila Proteins
  • Extracellular Matrix Proteins
  • Hexosamines
  • Epidermal Growth Factor
  • Eogt protein, Drosophila
  • N-Acetylglucosaminyltransferases
  • O-GlcNAc transferase
  • Acetylglucosamine