GlcNAc6ST3 is a keratan sulfate sulfotransferase for the protein-tyrosine phosphatase PTPRZ in the adult brain

Sci Rep. 2019 Mar 13;9(1):4387. doi: 10.1038/s41598-019-40901-2.

Abstract

Keratan sulfate (KS) is a carbohydrate side chain covalently attached to extracellular proteoglycans. KS is composed of disaccharide units of 6-sulfated N-acetylglucosamine (GlcNAc) and galactose. We have previously shown that GlcNAc-6-O-sulfotransferase (GlcNAc6ST) 1 encoded by Chst2 is an enzyme necessary for the synthesis of GlcNAc-6-sulfated KS chains that are required for neuronal plasticity in the visual cortex of the mouse brain during the critical period, but not in adulthood. Here, we show that GlcNAc-6-sulfated KS recognized by the R-10G anti-KS antibody, of which the minimum epitope structure is Galß1-4GlcNAc(6S)ß1-3Galß1-4GlcNAc(6S), distributes diffusely in neuropils and presents densely in close proximity to the perineuronal region of the perineuronal net (PNN)-positive neurons in the adult visual cortex. Surprisingly, GlcNAc6ST3, which was discovered as an intestinal GlcNAc6ST encoded by Chst5, is a major brain KS sulfotransferase expressed in oligodendrocytes in adulthood. Moreover, we identified an isoform of the protein-tyrosine phosphatase PTPRZ as a R-10G-reactive KS proteoglycan. These results indicate that GlcNAc6ST3 may play a role in synthesis of a component of PNN in the adult brain, and that the KS-modified isoform of PTPRZ encoded by Ptprz1 could be an extracellular molecule associated with PNNs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / enzymology*
  • Brain / metabolism*
  • Carbohydrate Sulfotransferases
  • Female
  • Immunoprecipitation
  • Keratan Sulfate / metabolism*
  • Male
  • Mice
  • Microscopy, Confocal
  • Protein Tyrosine Phosphatases
  • Proteoglycans / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism*
  • Sulfotransferases / metabolism*
  • Synaptophysin / metabolism

Substances

  • Proteoglycans
  • Synaptophysin
  • Keratan Sulfate
  • Sulfotransferases
  • Protein Tyrosine Phosphatases
  • Ptprz1 protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5