Glycosylation, galectins and cellular signaling
Glycosylation, galectins and cellular signaling
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DOI：
10.1016/j.ceb.2011.05.001
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发表时间：
2011-08-01
影响因子：
7.5
通讯作者：
Nabi, Ivan R.
中科院分区：
文献类型：
--
作者：
Boscher, Cecile;Dennis, James W.;Nabi, Ivan R.
糖基化是分泌途径的蛋白质和脂质的常见翻译后修饰，其产生半乳糖特异性凝集素或半乳糖凝集素的结合位点。通过N-乙酰葡糖胺转移酶（Mgat基因）使Asn连接的（N-）聚糖分支增加对半乳糖凝集素的亲和力。酶的组织特异性表达和糖-核苷酸向ER和高尔基体的代谢供应调节聚糖分布，而蛋白质序列指定NXS/T位点多样性，为半乳糖凝集素-糖蛋白相互作用提供代谢和遗传贡献。半乳糖凝集素交联糖蛋白形成动态微结构域或晶格，其调节细胞粘附、迁移、增殖、存活和分化的各种介质。在C.线虫和人类，但更高亲和力的分支N-聚糖的表达是脊椎动物进化的最新特征。半乳糖凝集素可被认为是蛋白质中最小结合单位[Gal（NAc）β 1-3/4GilcNAc]和NXS/T位点多样性重复的阅读代码。快速发展和结构复杂的高尔基体修饰表面受体解释通过亲和力的晶格，调节受体水平的细胞环境的功能，从而各种细胞命运的概率。关于半乳糖凝集素、聚糖配体以及与其他膜结构域和内吞途径的晶格相互作用的调节，仍存在许多重要的问题。
Glycosylation is a common posttranslational modification of proteins and lipids of the secretory pathway that generates binding sites for galactose-specific lectins or galectins. Branching of Asn-linked (N-)glycans by the N-acetylglucosaminyltransferases (Mgat genes) increases affinity for galectins. Both tissue-specific expressior of the enzymes and the metabolic supply of sugar-nucleotides to the ER and Golgi regulate glycan distribution while protein sequences specify NXS/T site multiplicity, providing metabolic and genetic contributions to galectin-glycoprotein interactions. Galectins cross-link glycoproteins forming dynamic microdomains or lattices that regulate various mediators of cell adhesion, migration, proliferation, survival and differentiation. There are a similar number of galactose-specific galectins in C. elegans and humans, but expression of higher-affinity branched N-glycans are a more recent feature of vertebrate evolution. Galectins might be considered a reading code for repetition of the minimal units of binding [Gal(NAc)beta 1-3/4GilcNAc] and NXS/T site multiplicity in proteins. The rapidly evolving and structurally complex Golgi modifications to surface receptors are interpreted through affinity for the lattice, which regulates receptor levels as a function of the cellular environment, and thereby the probability of various cell fates. Many important questions remain concerning the regulation of the galectins, the glycan ligands and lattice interaction with other membrane domains and endocytic pathways.