Carbohydrate-to-carbohydrate interaction, through glycosynapse, as a basis of cell recognition and membrane organization

Carbohydrate-to-carbohydrate interaction, through glycosynapse, as a basis of cell recognition and membrane organization
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DOI:
10.1023/b:glyc.0000044844.95878.cf
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发表时间:
2004-01-01
影响因子:
3
通讯作者:
Hakomori, S
Hakomori, S
中科院分区:
生物学4区
文献类型:
--
作者:
Hakomori, S

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由碳水化合物与碳水化合物相互作用(CCI)介导的细胞黏附,或具有并发信号转导的细胞黏附,在三个上下文中被讨论1。对基于几种糖鞘糖脂(GSLs)在界面细胞表面相互作用(“反式相互作用”)的细胞黏附类型进行了严格的综述,以排除GSL结合蛋白的可能参与。特别强调:(I)Lex-to-Lex相互作用介导的小鼠畸胎癌F9细胞的自我聚集,其中排除Lex结合蛋白的存在;(Ii)表达GM3的细胞与表达GG3的细胞的黏附,其中排除GM3或GG3结合蛋白的参与。总结了CCI与碳水化合物-蛋白质相互作用(CPI)和蛋白质-蛋白质相互作用(PPI)的特点和要求,包括:(1)二价阳离子的专一性和要求;(2)CCI相对于PPI的反应速度;(3)负(排斥)相互作用;(4)CCI和PPI的协同或协同作用,特别是GM3-GG3或GM3-LacCer相互作用与整合素依赖的黏附,或Lex-Lex与E-钙粘素依赖的黏附的协同作用。细胞表面的微区是基于GSLS或糖蛋白的聚集而形成的,这些糖蛋白通过信号转导而组织起来。在这些微域中,那些参与黏附和信号转导以改变细胞表型的微域被称为“糖突触”。在一些糖类突触中,生长因子受体或整合素受体也参与其中,只有当受体被N-糖基化时,它们的功能才受到GSLS的调节。这种调节可能部分地通过GSLS与受体的N-连接的糖链的相互作用而发生,称为“顺式相互作用”。
Cell adhesion mediated by carbohydrate-to-carbohydrate interaction (CCI), or cell adhesion with concurrent signal transduction, are discussed in three contexts.1. Types of cell adhesion based on interaction of several combinations of glycosphingolipids (GSLs) at the surface of interfacing cells ("trans interaction") are reviewed critically, to exclude the possible involvement of GSL-binding proteins. Special emphasis is on: (i) autoaggregation of mouse teratocarcinoma F9 cells mediated by Lex-to-Lex interaction, in which presence of Lex-binding protein is ruled out; (ii) adhesion of GM3-expressing cells to Gg3-expressing cells, in which involvement of GM3- or Gg3-binding protein is ruled out.2. Characteristic features and requirements of CCI, as compared with carbohydrate-to-protein interaction (CPI) and protein-to-protein interaction (PPI), are summarized, including: (i) specificity and requirement of bivalent cation; (ii) reaction velocity of CCI as compared to PPI; (iii) negative (repulsive) interaction; (iv) synergistic or cooperative effect of CCI and PPI, particularly GM3-to-Gg3 or GM3-to-LacCer interaction in synergy with integrin-dependent adhesion, or Lex-to-Lex interaction in cooperation with E-cadherin-dependent adhesion.3. Microdomains at the cell surface are formed based on clustering of GSLs or glycoproteins organized with signal transducers. Among such microdomains, those involved in adhesion coupled with signal transduction to alter cellular phenotype are termed "glycosynapse". In some glycosynapses, growth factor receptors or integrin receptors are also involved, and their function is modulated by GSLs only when the receptor is N-glycosylated. This modulation may occur in part via interaction of GSLs with N-linked glycans of the receptor, termed "cis interaction".