Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains
Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains
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DOI：
10.1016/j.bbagen.2007.10.008
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发表时间：
2008-03-01
影响因子：
3
通讯作者：
Hakomori, Sen-Itiroh
中科院分区：
文献类型：
--
作者：
Todeschini, Adriane Regina;Hakomori, Sen-Itiroh
在细胞表面微区，由鞘糖脂、N-或O-连接寡糖携带的糖基表位被碳水化合物结合蛋白或互补碳水化合物识别。在这两种情况下，碳水化合物表位可能与特定的信号转导器、四跨膜蛋白、粘附受体或生长因子受体聚集。通过这个框架，碳水化合物可以介导细胞信号传导，导致细胞表型的变化。参与诱导细胞活化、运动和生长的碳水化合物依赖性细胞粘附的微结构域被称为“糖突触”。在这篇综述中，提出了导致糖突触概念的富含鞘糖脂的微域研究的历史概要。糖突触作为控制肿瘤细胞表型的信号单元的例子在三个方面进行了讨论：（i）通过头对头（反式）碳水化合物与碳水化合物相互作用，由接口糖突触结构域之间的鞘糖脂与鞘糖脂相互作用介导的细胞与细胞粘附。 (ii)GM3与四跨膜蛋白CD9复合的功能作用，以及这种复合物与整联蛋白或与成纤维细胞生长因子受体的相互作用，以控制肿瘤细胞表型及其向正常细胞表型的回复。 (iii) 糖突触微域中的 GM2/四跨膜蛋白 CD82 复合物对整合素依赖性 Met 激酶活性的抑制。这里的数据表明，糖突触的组织状态强烈影响细胞表型，从而影响肿瘤细胞的恶性程度。 (c) 2007 Elsevier B.V. 保留所有权利。
At cell surface microdomains, glycosyl epitopes, carried either by glycosphingolipids, N- or O-linked oligosaccharides, are recognized by carbohydrate-binding proteins or complementary carbohydrates. In both cases, the carbohydrate epitopes may be clustered with specific signal transducers, tetraspanins, adhesion receptors or growth factor receptors. Through this framework, carbohydrates can mediate cell signaling leading to changes in cellular phenotype. Microdomains involved in carbohydrate-dependent cell adhesion inducing cell activation, motility, and growth are termed "glycosynapse". In this review a historical synopsis of glycosphingolipids-enriched microdomains study leading to the concept of glycosynapse is presented. Examples of glycosynapse as signaling unit controlling the tumor cell phenotype are discussed in three contexts: (i) Cellto-cell adhesion mediated by glycosphingolipids-to-glycosphingolipids interaction between interfacing glycosynaptic domains, through head-tohead (trans) carbohydrate-to-carbohydrate interaction. (ii) Functional role of GM3 complexed with tetraspanin CD9, and interaction of such complex with integrins, or with fibroblast growth factor receptor, to control tumor cell phenotype and its reversion to normal cell phenotype. (iii) Inhibition of integrin-dependent Met kinase activity by GM2/tetraspanin CD82 complex in glycosynaptic microdomain. Data present here suggest that the organizational status of glycosynapse strongly affects cellular phenotype influencing tumor cell malignancy. (c) 2007 Elsevier B.V. All rights reserved.