Giantin-knockout models reveal a feedback loop between Golgi function and glycosyltransferase expression

J Cell Sci. 2017 Dec 15;130(24):4132-4143. doi: 10.1242/jcs.212308. Epub 2017 Nov 1.

Abstract

The Golgi is the cellular hub for complex glycosylation, controlling accurate processing of complex proteoglycans, receptors, ligands and glycolipids. Its structure and organisation are dependent on golgins, which tether cisternal membranes and incoming transport vesicles. Here, we show that knockout of the largest golgin, giantin, leads to substantial changes in gene expression but only limited effects on Golgi structure. Notably, 22 Golgi-resident glycosyltransferases, but not glycan-processing enzymes or the ER glycosylation machinery, are differentially expressed following giantin ablation. This includes near-complete loss of function of GALNT3 in both mammalian cell and zebrafish models. Giantin-knockout zebrafish exhibit hyperostosis and ectopic calcium deposits, recapitulating phenotypes of hyperphosphatemic familial tumoral calcinosis, a disease caused by mutations in GALNT3. These data reveal a new feature of Golgi homeostasis: the ability to regulate glycosyltransferase expression to generate a functional proteoglycome.

Keywords: GALNT3; Giantin; Glycosylation; Golgi; Hyperphosphatemic tumoral calcinosis; Zebrafish.

MeSH terms

  • Animals
  • Cell Line
  • Gene Expression Regulation, Enzymologic
  • Glycosyltransferases / genetics*
  • Golgi Apparatus / enzymology
  • Golgi Apparatus / genetics*
  • Golgi Matrix Proteins
  • Humans
  • Membrane Proteins / genetics*
  • Mutation
  • N-Acetylgalactosaminyltransferases / genetics*
  • Polypeptide N-acetylgalactosaminyltransferase
  • Zebrafish

Substances

  • Golgi Matrix Proteins
  • Membrane Proteins
  • macrogolgin
  • Glycosyltransferases
  • N-Acetylgalactosaminyltransferases