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

Nicola L. Stevenson, Dylan J.M. Bergen, Roderick E.H. Skinner, Erika Kague, Elizabeth Martin-Silverstone, Kate A. Robson Brown, Chrissy L. Hammond, David J. Stephens*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

14 Citations (Scopus)
256 Downloads (Pure)

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, 22Golgi-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 bothmammalian 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.

Original languageEnglish
Pages (from-to)4132-4143
Number of pages12
JournalJournal of Cell Science
Volume130
Issue number24
Early online date1 Nov 2017
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • GALNT3
  • Giantin
  • Glycosylation
  • Golgi
  • Hyperphosphatemic tumoral calcinosis
  • Zebrafish

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