PDF(Pubmed)
Abstract：
Glycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident N-glycans participate with the Glc3Man9GlcNAc2 highly conserved sequence, in protein folding process, where the physiological balance between glycosylation/deglycosylation on the innermost glucose residue takes place, according GANAB/UGGT concentration ratio. However, under abnormal conditions, the cell adapts to the glucose availability by adopting an aerobic or anaerobic regimen of glycolysis, or to external stimuli through internal or external recognition patterns, so it responds to pathogenic noxa with unfolded protein response (UPR). UPR can affect Multiple Sclerosis (MS) and several neurological and metabolic diseases via the BiP stress sensor, resulting in ATF6, PERK and IRE1 activation. Furthermore, the abnormal GANAB expression has been observed in MS, systemic lupus erythematous, male germinal epithelium and predisposed highly replicating cells of the kidney tubules and bile ducts. The latter is the case of Polycystic Liver Disease (PCLD) and Polycystic Kidney Disease (PCKD), where genetically induced GANAB loss affects polycystin-1 (PC1) and polycystin-2 (PC2), resulting in altered protein quality control and cyst formation phenomenon. Our topics resume the role of glycans in cell physiology, highlighting the N-glycans one, as a substrate of GANAB, which is an emerging key molecule in MS and other human pathologies.
摘要：
聚糖是生物物质的四个基本大分子成分之一，它们在细胞中受到高度调节。它们的功能是代谢，结构和调制。特别是,ER常驻N-聚糖参与Glc3Man9GlcNAc2高度保守的序列，在蛋白质折叠过程中，在最内层葡萄糖残基上发生糖基化/去糖基化之间的生理平衡，根据GANAB/UGGT浓度比。然而,在异常情况下，细胞通过采用有氧或无氧糖酵解方案来适应葡萄糖的可用性，或通过内部或外部识别模式的外部刺激，所以它对致病性noxa有未折叠的蛋白反应（UPR）。UPR可以通过BiP应力传感器影响多发性硬化（MS）和几种神经和代谢性疾病，导致ATF6、PERK和IRE1激活。此外，在MS中观察到GANAB表达异常，系统性红斑狼疮,男性生发上皮和肾小管和胆管的易感高度复制细胞。后者是多囊性肝病（PCLD）和多囊性肾病（PCKD），其中遗传诱导的GANAB损失影响多囊藻毒素-1（PC1）和多囊藻毒素-2（PC2），导致蛋白质质量控制改变和囊肿形成现象。我们的主题恢复聚糖在细胞生理学中的作用，突出显示N-聚糖，作为GANAB的底物，这是MS和其他人类病理中新兴的关键分子。
