A validated collection of mouse monoclonal antibodies to human glycosyltransferases functioning in mucin-type O-glycosylation

Glycobiology. 2019 Aug 20;29(9):645-656. doi: 10.1093/glycob/cwz041.

Abstract

Complex carbohydrates serve a wide range of biological functions in cells and tissues, and their biosynthesis involves more than 200 distinct glycosyltransferases (GTfs) in human cells. The kinetic properties, cellular expression patterns and subcellular topology of the GTfs direct the glycosylation capacity of a cell. Most GTfs are ER or Golgi resident enzymes, and their specific subcellular localization is believed to be distributed in the secretory pathway according to their sequential role in the glycosylation process, although detailed knowledge for individual enzymes is still highly fragmented. Progress in quantitative transcriptome and proteome analyses has greatly advanced our understanding of the cellular expression of this class of enzymes, but availability of appropriate antibodies for in situ monitoring of expression and subcellular topology have generally been limited. We have previously used catalytically active GTfs produced as recombinant truncated secreted proteins in insect cells for generation of mouse monoclonal antibodies (mAbs) to human enzymes primarily involved in mucin-type O-glycosylation. These mAbs can be used to probe subcellular topology of active GTfs in cells and tissues as well as their presence in body fluids. Here, we present several new mAbs to human GTfs and provide a summary of our entire collection of mAbs, available to the community. Moreover, we present validation of specificity for many of our mAbs using human cell lines with CRISPR/Cas9 or zinc finger nuclease (ZFN) knockout and knockin of relevant GTfs.

Keywords: CRISPR Cas9; GalNAc-transferase; immunocytology; immunohistology; western blot.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibody Specificity*
  • Glycosylation
  • Glycosyltransferases / deficiency
  • Glycosyltransferases / genetics
  • Glycosyltransferases / immunology*
  • Glycosyltransferases / metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • Mucins / metabolism*
  • Reproducibility of Results

Substances

  • Antibodies, Monoclonal
  • Mucins
  • Glycosyltransferases