Nieminen Julie, Kuno Atsushi, Hirabayashi Jun, Sato Sachiko
Glycobiology Laboratory, Research Centre for Infectious Diseases, Faculty of Medicine, Laval University, Québec G1V 4G2, Canada.
J Biol Chem. 2007 Jan 12;282(2):1374-83. doi: 10.1074/jbc.M604506200. Epub 2006 Nov 2.
Galectin-3, a member of the galectin family of carbohydrate binding proteins, is widely expressed, particularly in cells involved in the immune response. Galectin-3 has also been indicated to play a role in various biological activities ranging from cell repression to cell activation and adhesion and has, thus, been recognized as an immunomodulator. Whereas those activities are likely to be associated with ligand cross-linking by this lectin, galectin-3, unlike other members of the galectin family, exists as a monomer. It has consequently been proposed that oligomerization of the N-terminal domains of galectin-3 molecules, after ligand binding by the C-terminal domain, is responsible for this cross-linking. The oligomerization status of galectin-3 could, thus, control the majority of its extracellular activities. However, little is known about the actual mode of action through which galectin-3 exerts its function. In this report we present data suggesting that oligomerization of galectin-3 molecules occurs on cell surfaces with physiological concentrations of the lectin. Using galectin-3 labeled at the C terminus with Alexa 488 or Alexa 555, the oligomerization between galectin-3 molecules on cell surfaces was detected using fluorescence resonance energy transfer. We observed this fluorescence resonance energy transfer signal in different biological settings representing the different modes of action of galectin-3 that we previously proposed; that is, ligand crosslinking leading to cell activation, cell-cell interaction/adhesion, and lattice formation. Furthermore, our data suggest that galectin-3 lattices are robust and could, thus, be involved, as previously proposed, in the restriction of receptor clustering.
半乳糖凝集素-3是碳水化合物结合蛋白半乳糖凝集素家族的成员之一，广泛表达，尤其在参与免疫反应的细胞中。半乳糖凝集素-3也被认为在从细胞抑制到细胞激活和黏附等各种生物活性中发挥作用，因此被视为一种免疫调节剂。虽然这些活性可能与该凝集素的配体交联有关，但与半乳糖凝集素家族的其他成员不同，半乳糖凝集素-3以单体形式存在。因此有人提出，在C端结构域与配体结合后，半乳糖凝集素-3分子N端结构域的寡聚化负责这种交联。因此，半乳糖凝集素-3的寡聚化状态可能控制其大部分细胞外活性。然而，关于半乳糖凝集素-3发挥其功能的实际作用方式知之甚少。在本报告中，我们提供的数据表明，在生理浓度的凝集素条件下，半乳糖凝集素-3分子在细胞表面发生寡聚化。使用在C端用Alexa 488或Alexa 555标记的半乳糖凝集素-3，通过荧光共振能量转移检测细胞表面半乳糖凝集素-3分子之间的寡聚化。我们在不同的生物学环境中观察到了这种荧光共振能量转移信号，这些环境代表了我们之前提出的半乳糖凝集素-3的不同作用模式；即配体交联导致细胞激活、细胞-细胞相互作用/黏附以及晶格形成。此外，我们的数据表明，半乳糖凝集素-3晶格很稳定，因此可能如之前所提出的那样，参与受体聚集的限制。
