Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation
Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation
复制标题
DOI：
10.1016/j.cell.2007.01.049
复制
发表时间：
2007-04-06
期刊：
影响因子：
64.5
通讯作者：
Dennis, James W.
中科院分区：
文献类型：
--
作者：
Lau, Ken S.;Partridge, Emily A.;Dennis, James W.
N-聚糖的数量（n）是每个糖蛋白序列的独特特征，并与高尔基体N-聚糖分支途径的物理性质合作，以调节表面糖蛋白水平。高尔基体途径对氨基己糖通量超敏感，用于产生三触角和四触角N-聚糖，其结合半乳糖凝集素并形成分子晶格，对抗糖蛋白内吞作用。具有很少N-聚糖的糖蛋白（例如，T β R、CTLA-4和GLUT 4）表现出对增加的己糖胺浓度具有开关样应答的增强的细胞表面表达，而具有大量N-聚糖的糖蛋白（例如，EGFR、IGFR、FGFR和PDGFR）表现出双曲线响应。计算和实验数据表明，这些功能允许营养通量刺激生长促进高n受体驱动逮捕/分化程序，通过增加低n糖蛋白的表面水平。我们已经确定了一种机制，代谢调节细胞之间的过渡生长和逮捕哺乳动物所产生的N-聚糖数量和分支的明显的共同进化。
The number of N-glycans (n) is a distinct feature of each glycoprotein sequence and cooperates with the physical properties of the Golgi N-glycan-branching pathway to regulate surface glycoprotein levels. The Golgi pathway is ultrasensitive to hexosamine flux for the production of tri- and tetra-antennary N-glycans, which bind to galectins and form a molecular lattice that opposes glycoprotein endocytosis. Glycoproteins with few N-glycans (e.g., T beta R, CTLA-4, and GLUT4) exhibit enhanced cell-surface expression with switch-like responses to increasing hexosamine concentration, whereas glycoproteins with high numbers of N-glycans (e.g., EGFR, IGFR, FGFR, and PDGFR) exhibit hyperbolic responses. Computational and experimental data reveal that these features allow nutrient flux stimulated by growth-promoting high-n receptors to drive arrest/differentiation programs by increasing surface levels of low-n glycoproteins. We have identified a mechanism for metabolic regulation of cellular transition between growth and arrest in mammals arising from apparent coevolution of N-glycan number and branching.