N-聚糖和O-聚糖在极性化细胞蛋白质分拣中的作用

Role of N-glycans and O-glycans in Polarized Sorting of Protein

极性化上皮细胞的质膜因其所含蛋白质、脂质等组分不同,可以分为细胞膜顶端和细胞膜基底侧端两个区域,而新合成的蛋白质向这两个区域的有效分拣是上皮细胞维持其自身极性及正常功能所必需的。细胞膜基底侧端蛋白质的分拣主要由位于该蛋白质胞质区的信号肽所介导,关于这方面的研究是比较深入的;而细胞膜顶端蛋白质的分拣机制目前尚未阐明,因而显得比较复杂。近年来,糖类分子作为生物体内细胞识别和调控过程的信息分子日益受到关注,人们通过干扰聚糖合成、基因突变以及构建糖基化缺陷细胞株等实验方法,逐渐地认识到糖类分子在极性化上皮细胞的蛋白质分拣调节中起重要作用。由于糖分子本身结构非常复杂,而且目前缺乏研究糖类分子的有效手段,使得糖生物学的研究远远落后于蛋白质和核酸的研究。从而导致探讨糖类分子在蛋白质分拣过程的具体机制相对来说比较困难。本综述拟简要概括糖类分子中N-聚糖和O-聚糖在极性化上皮细胞的蛋白质分拣过程中的作用,以及两种聚糖在此过程中行使分拣信号功能的可能机制。

The plasma membrane of polarized epithelial cell is divided into apical and basolateral subdomains by distinct protein and lipid compositions. Maintenance of polarity and proper function require efficient sorting of newly synthesized proteins to the apical and basolateral surfaces of cells. Basolateral protein is sorted by the sorting signals located in the cytoplasmic domain. Contrasting sharply, the sorting of apical proteins is thought to be sorted by lipid rafts which are less well known and therefore becomes so complicated. Polymeric glycans have been attracting extensive attentions as signal molecule of cell recognization and signal transduction. By means of glycosylation perturbants, mutagenesis, RNA interference and glycosylation-deficient cell lines, role of N-and O-linked glycans has been gradually known as polarized sorting determinants in recent years. Because the structures of glycans are extraordinarily diverse and no effective means are emerging, research on glycobiology falls behind protein and nucleic acid. This challenges the investigation of the mechanism of N-or O-glycarts in polarized sorting in epithelial cells.However,some authors have recendy proposed several hypotheses that glycans act as polarized sorting signals. This review briefly summarizes the role of N- and O-linked glycans during the pathway of polarized sorting, and discusses possible mechanisms for how these glycans might function as sorting signals in polarized epithelial ceils.