RT Journal Article SR Electronic T1 Giantin knockout models reveal the capacity of the Golgi to regulate its biochemistry by controlling glycosyltransferase expression JF bioRxiv FD Cold Spring Harbor Laboratory SP 123547 DO 10.1101/123547 A1 Nicola L. Stevenson A1 Dylan J. M. Bergen A1 Roderick E. H. Skinner A1 Kate A. Robson Brown A1 Chrissy L. Hammond A1 David J. Stephens YR 2017 UL http://biorxiv.org/content/early/2017/04/03/123547.abstract AB The Golgi is the cellular hub for glycosylation, controlling accurate processing of complex proteoglycans 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. Most of these glycosyltransferases are highly downregulated following genetic knockout of giantin, including a near-complete loss of expression of GALNT3 in both mammalian cell and zebrafish models. Furthermore, knockout zebrafish exhibit increased bone mass density, hyperostosis, and ectopic calcium deposits recapitulating phenotypes of hyperphosphatemic familial tumoral calcinosis, a disease caused by mutations in GALNT3. Our data reveal a new feature of Golgi homeostasis, the ability to regulate glycosyltransferase expression to generate a functional proteoglycome.