Cell Biology Laboratories, School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
J Cell Sci. 2017 Dec 15;130(24):4132-4143. doi: 10.1242/jcs.212308. Epub 2017 Nov 1.
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.
高尔基复合体是细胞内糖基化的核心，负责精确加工复杂蛋白聚糖、受体、配体和糖脂。其结构和组织取决于高尔基器相关蛋白，后者可将膜囊和输入的转运小泡锚定在高尔基复合体上。本文中，我们发现最大的高尔基器相关蛋白 giantin 的敲除会导致基因表达发生显著变化，但对高尔基复合体结构的影响有限。值得注意的是，ginatn 缺失后，22 种定位于高尔基复合体的糖基转移酶而非糖基化加工酶或内质网糖基化机制发生差异表达，包括哺乳动物细胞和斑马鱼模型中 GALNT3 功能几乎完全丧失。高尔基复合体 giantin 敲除的斑马鱼表现出骨过度生长和异位钙沉积，这再现了由 GALNT3 基因突变引起的高磷酸血症家族性肿瘤性钙沉着症的表型。这些数据揭示了高尔基复合体稳态的一个新特征：能够调节糖基转移酶表达以产生功能性蛋白聚糖组。
