Modulation of neuraminidase activity by the physical state of phospholipid bilayers containing gangliosides Gd1a and Gt1b.
Modulation of neuraminidase activity by the physical state of phospholipid bilayers containing gangliosides Gd1a and Gt1b.
复制标题
通过含有神经节苷脂 Gd1a 和 Gt1b 的磷脂双层的物理状态调节神经氨酸酶活性。
DOI：
10.1021/bi00302a016
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发表时间：
1984
期刊：
影响因子：
2.9
通讯作者：
Freire,E
中科院分区：
文献类型：
--
作者：
Myers,M;Wortman,C;Freire,E
Melanie Myers，Cora Wortman和Ernesto Freire* 摘要：通过使用高灵敏度差示扫描量热法和稳态荧光光谱，研究了在其外表面上含有二唾液酸神经节苷脂Gdla和三唾液酸神经节苷脂Gtlb的大单层二棕榈酰磷脂酰胆碱囊泡的热致行为，其为神经节苷脂摩尔分数和Ca 2+浓度的函数。这些研究表明，这两个神经节苷脂有一个有序的双层的碳氢化合物区域的效果，这种效果是增强的存在下的Ca 2+离子。量热实验还表明，神经节苷脂Gtlb有一个内在的趋势相分离成成分丰富的神经节苷脂域，即使在没有Ca 2+。另一方面，神经节苷脂Gdla仅在Ca 2+浓度等于或高于10 mM时发生相分离。这些研究使我们能够确定和评估影响神经节苷脂水解速率的因素（神经节苷脂是位于质膜外表面和中枢神经系统突触膜中的含有糖鞘脂的复合唾液酸（Leidon，1978）。它们参与多种细胞表面相关过程，如作为蛋白质激素的受体参与细胞的识别机制（如促甲状腺激素）、细菌毒素（如霍乱毒素、破伤风毒素）、干扰素和纤连蛋白，以及病毒感染的机制（货车Heyningen，1974; Fishman和布雷迪，1976; Lai，1980; Rodgers & Snyder，1981; Markwell等人，1981年）。也有报道称，细胞的恶性转化有时与神经节苷脂成分的改变有关（Wallach，1975）。导致某些神经节苷脂积聚的代谢性疾病，例如泰-萨克斯病或GM、神经节苷脂沉积症，会导致智力低下（布雷迪，1982）。尽管神经节苷脂在细胞表面现象中起重要作用，但关于它们的功能方式、与配体分子缔合的分子机制、它们与其他膜组分的相互作用、以及膜结构和物理参数对这些相互作用的调节。由于神经节苷脂与各种膜外底物和酶如唾液酸转移酶和神经氨酸酶相互作用，因此了解这些相互作用如何受到膜物理参数如脂质组成、脂质流动性或神经节苷脂组成结构域沿着膜表面形成的影响是至关重要的。在本文中，我们提出了一项研究的结果，旨在阐明影响
Melanie Myers, Cora Wortman, and Ernesto Freire* abstract: The thermotropic behavior of large unilamellar dipalmitoylphosphatidylcholine vesicles containing the di-sialoganglioside Gdla and the trisialoganglioside Gtlb on their outer surface has been studied as a function of the ganglioside molar fraction and Ca2+ concentration by using high-sensitivity differential scanning calorimetry and steady-state fluorescence spectroscopy. These studies indicate that both gangliosides have an ordering effect on the hydrocarbon region of the bilayer and that this effect is enhanced by the presence of Ca2+ ions. The calorimetric experiments also indicate that gang-lioside Gtlb has an intrinsic tendency to phase separate into compositional-rich ganglioside domains even in the absence of Ca2+. Ganglioside Gdla, on the other hand, only phase separates at Ca2+ concentrations equalto or higher than 10 mM. These studies have allowed us to identify and evaluate the factors affecting the rates of hydrolysis of gangliosides by (jangliosides are complex sialic acid containing glyco-sphingolipids located in the outer surface of plasma membranes and in the synaptic membranes of the central nervous system (Ledeen, 1978). They have been implicated in a variety of cell surface related processes such as in the recognition ma-chinery of the cell, as receptors for protein hormones (eg, thyroid stimulating hormone), bacterial toxins (eg, cholera-toxin, tetanus toxin), interferon, and fibronectin, and in the mechanism of viralinfection (Van Heyningen, 1974; Fishman & Brady, 1976; Lai, 1980; Rodgers & Snyder, 1981; Markwell et al., 1981). It has also been reported that the malignant transformation of cells is sometimes associated with an altered ganglioside composition (Wallach, 1975). Metabolic disorders resulting in the accumulation of certain gangliosidessuch as Tay-Sachs disease or GM, gangliosidosis result in mental retardation (Brady, 1982).Despite the important role of gangliosides in cell-surface phenomena, very little is known regarding the way they function, the molecular mechanisms of association with ligand molecules, their interactions with other membranecomponents, and the modulation of these interactions by membrane structural and physical parameters. Since gangliosides interact with a variety of extramembranous substrates and enzymes like sialyltransferases and neuraminidases, it is of primary importance to understand how these interactions are affected by membrane physical parameters such as lipid composition, lipid fluidity, or the formation of ganglioside compositional domains along the membrane surface. In this paper, we present the results of a study directed to elucidate the influence