Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Journal of cell science, 2017-12, Vol.130 (24), p.4132-4143

Ort / Verlag

England: The Company of Biologists Ltd

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Electronic Journals Library - Freely accessible e-journals

Beschreibungen/Notizen

• 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.