Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Mol Aspects Med. 2016 Oct;51:89-103. doi: 10.1016/j.mam.2016.05.004. Epub 2016 May 26.
N-glycans on glycoproteins serve as one of the most important co- and post-translational modifications of proteins, and it has been well established that they play pivotal roles in controlling the physicochemical and/or physiological properties of the carrier proteins. The biosynthetic/processing pathways for N-glycans have been well characterized in mammalian cells. There are, however, issues that remain to be clarified concerning aspects of their degradation. While the molecular mechanism of the lysosomal degradation for N-glycoproteins has been well studied in relation to genetic disorders, which are collectively referred to as lysosomal storage disorders, evidence exists to suggest that there are also "non-lysosomal" degradation processes, which are now known to occur widely in eukaryotic cells. In this review, our current knowledge of the lysosomal/non-lysosomal degradation of N-glycoproteins in mammalian cells, as well as in human genetic disorders caused by the defects of these processes, is reviewed.
糖蛋白上的 N-糖链是蛋白质翻译后修饰的重要方式之一，其对糖蛋白的理化性质和/或生理功能具有重要的调控作用。糖基化修饰的生物合成/加工途径在哺乳动物细胞中已经得到了很好的阐述，但在 N-糖链的降解方面仍存在一些需要阐明的问题。尽管溶酶体降解 N-糖蛋白的分子机制已在遗传疾病（统称为溶酶体贮积症）的研究中得到了很好的研究，但有证据表明还存在“非溶酶体”降解途径，这些途径现已在真核细胞中广泛存在。在这篇综述中，我们回顾了哺乳动物细胞中 N-糖蛋白的溶酶体/非溶酶体降解以及这些过程缺陷引起的人类遗传疾病的相关知识。
