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Publication - Professor Katharine Robson Brown

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

    Citation

    Stevenson, N, Bergen, D, Skinner, R, Kague, E, Martin-Silverstone, E, Brown, KAR, Hammond, C & Stephens, D, 2017, ‘Giantin knockout models reveal a feedback loop between Golgi function and glycosyltransferase expression’. Journal of Cell Science, vol 130., pp. 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.

    Full details in the University publications repository