PUBLICATION
Giantin knockout models reveal a feedback loop between Golgi function and glycosyltransferase expression
- Authors
- Stevenson, N.L., Bergen, D.J.M., Skinner, R.E.H., Kague, E., Martin-Silverstone, E., Robson Brown, K.A., Hammond, C.L., Stephens, D.J.
- ID
- ZDB-PUB-171103-13
- Date
- 2017
- Source
- Journal of Cell Science 130(24): 4132-4143 (Journal)
- Registered Authors
- Bergen, Dylan, Hammond, Chrissy, Stephens, David, Stevenson, Nicola
- 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*
- Humans
- Membrane Proteins/genetics*
- Mutation
- N-Acetylgalactosaminyltransferases/genetics*
- Zebrafish
- PubMed
- 29093022 Full text @ J. Cell Sci.
Citation
Stevenson, N.L., Bergen, D.J.M., Skinner, R.E.H., Kague, E., Martin-Silverstone, E., Robson Brown, K.A., Hammond, C.L., Stephens, D.J. (2017) Giantin knockout models reveal a feedback loop between Golgi function and glycosyltransferase expression. Journal of Cell Science. 130(24):4132-4143.
Abstract
The Golgi is the cellular hub for complex glycosylation, controlling accurate processing of complex proteoglycans, receptors, ligands, and glycolipids. Its structure and organisation is 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 despite 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping