抑制高尔基体糖基化会导致内质网应激和蛋白质合成减少。
Inhibition of Golgi apparatus glycosylation causes endoplasmic reticulum stress and decreased protein synthesis.
机构信息
Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts 02118, USA.
出版信息
J Biol Chem. 2010 Aug 6;285(32):24600-8. doi: 10.1074/jbc.M110.134544. Epub 2010 Jun 7.
Abstract
Nucleotide sugar transporters of the Golgi apparatus play an essential role in the glycosylation of proteins, lipids, and proteoglycans. Down-regulation of expression of the transporters for CMP-sialic acid, GDP-fucose, or both unexpectedly resulted in accumulation of glycoconjugates in the Golgi apparatus rather than in the plasma membrane. Pulse-chase experiments with radiolabeled sugars and amino acids showed decreased synthesis and secretion of both nonglycoproteins and glycoproteins. Further studies revealed that the above silencing induced endoplasmic reticulum stress and inhibited protein translation initiation. Together these results suggest that global inhibition of Golgi apparatus glycosylation may lead to important secondary metabolic changes, unrelated to glycosylation.
摘要
高尔基体内核苷酸糖转运蛋白在蛋白质、脂质和蛋白聚糖的糖基化过程中发挥着重要作用。出人意料的是，下调 CMP-唾液酸、GDP-岩藻糖或两者的转运蛋白的表达水平，会导致糖缀合物在高尔基体内而不是在质膜中积累。用放射性标记的糖和氨基酸进行脉冲追踪实验表明，非糖蛋白和糖蛋白的合成和分泌都减少了。进一步的研究表明，上述沉默会诱导内质网应激，并抑制蛋白质翻译起始。这些结果表明，全面抑制高尔基体内糖基化可能会导致与糖基化无关的重要次级代谢变化。
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