How Adhesion/Growth-regulatory Galectins-1 and-3 Attain Cell Specificity: Case Study Defining Their Target on Neuroblastoma Cells (SK-N-MC) and Marked Affinity Regulation by Affecting Microdomain Organization of the Membrane
How Adhesion/Growth-regulatory Galectins-1 and-3 Attain Cell Specificity: Case Study Defining Their Target on Neuroblastoma Cells (SK-N-MC) and Marked Affinity Regulation by Affecting Microdomain Organization of the Membrane
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DOI：
10.1002/iub.358
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发表时间：
2010-08-01
期刊：
影响因子：
4.6
通讯作者：
Gabius, Hans-Joachim
中科院分区：
文献类型：
--
作者：
Kopitz, Juergen;Bergmann, Marion;Gabius, Hans-Joachim
凝集素是一种具有显著细胞类型特异性活性的有效效应器。它的发生对人类SK-N-MC神经母细胞瘤细胞参与负生长调节的潜在生化决定因素的性质提出了疑问。由于神经节苷脂GM1和同二聚体半乳糖凝集素-1的表面呈现增加先于生长抑制，因此建议直接相互作用。因此，我们研究了依赖于葡萄糖神经酰胺合成的细胞结合。它被n -丁基脱氧诺吉霉素和3- 1-苯基-2-癸烷氨基-3-morpholino-1-丙醇显著还原，为假设的凝集素/神经节苷脂结合提供了决定性的证据。糖蛋白不补偿神经节苷脂耗竭，这是通过测量脂结合唾液酸证实。通过破坏微域完整性，结合亲和力显著降低，对竞争性抑制剂半乳糖凝集素-3也有效。这是由2-羟丙基- β -环糊精或filipin III处理细胞引起的。在这个细胞系统中，靶特异性和配体呈递的拓扑结构共同作用，使高亲和力结合成为可能。(C) 2010 [j] .中国生物医学工程学报，62(8):624-628,2010
Galectins are potent effectors with conspicuous cell-type-specific activity profile. Its occurrence poses the question on the nature of the underlying biochemical determinants, in human SK-N-MC neuroblastoma cells involved in negative growth regulation. Since increase of surface presentation of ganglioside GM1 and homodimeric galectin-1 precedes growth inhibition, a direct interaction is suggested. We thus examined cell binding depending on glucosylceramide synthesis. It was drastically reduced by N-butyldeoxynojirimycin and threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, adding decisive evidence for the assumed galectin/ganglioside binding. Glycoproteins do not compensate ganglioside depletion which was verified by measuring lipid-bound sialic acid. Binding affinity is significantly lowered by disrupting microdomain integrity, also effective for the competitive inhibitor galectin-3. This was caused by cell treatment with either 2-hydroxypropyl-beta-cyclodextrin or filipin III. In this cell system, target specificity and topology of ligand presentation act together to enable high-affinity binding. (C) 2010 IUBMB IUBMB Life, 62(8): 624-628, 2010