Localisation to lipid rafts correlates with increased function of the Gal/GalNAc lectin in the human protozoan parasite, Entamoeba histolytica.
Localisation to lipid rafts correlates with increased function of the Gal/GalNAc lectin in the human protozoan parasite, Entamoeba histolytica.
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DOI：
10.1016/j.ijpara.2011.10.003
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发表时间：
2011-11
影响因子：
4
通讯作者：
Temesvari LA
中科院分区：
文献类型：
--
作者：
Welter BH;Goldston AM;Temesvari LA
溶组织内阿米巴是痢疾和肝脓肿的病原体，在发展中国家很流行。与宿主的粘附对感染至关重要，并由阿米巴表面受体介导。其中一种受体，Gal/GalNAc凝集素，与宿主成分上的半乳糖或n -乙酰半乳糖胺残基结合，由重亚基（Hgl）、轻亚基（Lgl）和中间亚基组成。凝集素组装成功能性复合体的机制尚不清楚。这种寄生虫也依赖于富含胆固醇的结构域（脂筏）来粘附。因此，可以想象木筏调节凝集素的组装或功能。为了验证这一点，变形虫装载了胆固醇和脂质筏被纯化和表征。Western blotting显示，胆固醇负荷导致筏中所有三个亚基的共区隔化。这种共区隔化伴随着变形虫以半乳糖特异性方式与宿主细胞结合能力的增强，这表明Gal/GalNAc凝集素的位置和功能之间存在相关性。胆固醇负荷并没有增加凝集素亚基的表面水平。因此，胆固醇诱导的黏附增加不是内部亚基池外化的结果。一个突变细胞系对胆固醇有轻微的反应，黏附轻微增加，在筏中只有轻微的Hgl和Lgl富集。这支持了Gal/GalNAc凝集素的位置和功能之间的联系。肌动蛋白也可以影响蛋白质与筏的相互作用。因此，用肌动蛋白解聚剂细胞松弛素D （cytochalasin D, CytoD）处理后，还评估了凝集素亚基的膜下分布。细胞d处理对亚基的膜下分布没有影响，这表明肌动蛋白不会阻止该系统中凝集素亚基与筏的结合。总之，这些数据提供了对调节这种粘附素的位置和功能的分子机制的见解。
Entamoeba histolytica is the causative agent of dysentery and liver abscess and is prevalent in developing countries. Adhesion to the host is critical to infection and is mediated by amoebic surface receptors. One such receptor, the Gal/GalNAc lectin, binds to galactose or N-acetylgalactosamine residues on host components and consists of heavy (Hgl), light (Lgl) and intermediate subunits. The mechanism by which the lectin assembles into a functional complex is not known. The parasite also relies on cholesterol-rich domains (lipid rafts) for adhesion. Therefore, it is conceivable that rafts regulate the assembly or function of the lectin. To test this, amoebae were loaded with cholesterol and lipid rafts were purified and characterized. Western blotting showed that cholesterol loading resulted in co-compartmentalization of all three subunits in rafts. This co-compartmentalization was accompanied by an increase in the ability of the amoebae to bind to host cells in a galactose-specific manner, suggesting that there is a correlation between location and function of the Gal/GalNAc lectin. Cholesterol loading did not increase the surface levels of the lectin subunits. Therefore, the cholesterol-induced increase in adhesion was not the result of externalization of an internal pool of subunits. A mutant cell line that modestly responded to cholesterol with a slight increase in adhesion exhibited only a slight enrichment of Hgl and Lgl in rafts. This supports the connection between location and function of the Gal/GalNAc lectin. Actin can also influence the interaction of proteins with rafts. Therefore, the sub-membrane distribution of the lectin subunits was also assessed after treatment with an actin depolymerizing agent, cytochalasin D (CytoD). CytoD-treatment had no effect on the submembrane distribution of the subunits, suggesting that actin does not prevent the association of lectin subunits with rafts in this system. Together, these data provide insight into the molecular mechanisms regulating the location and function of this adhesin.
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影响因子：
3.1
作者：
BRACHA, R;MIRELMAN, D
通讯作者：
MIRELMAN, D
影响因子：
3.3
作者：
Causeret, M;Taulet, N;Gauthier-Rouvière, C
通讯作者：
Gauthier-Rouvière, C
影响因子：
4
作者：
Blazquez, Samantha;Rigothier, Marie-Christine;Guillen, Nancy
通讯作者：
Guillen, Nancy
影响因子：
7.7
作者：
Mata-Cárdenas, BD;Vargas-Villarreal, J;Said-Fernández, S
通讯作者：
Said-Fernández, S
影响因子：
2.1
作者：
Mittal, K.;Welter, B. H.;Temesvari, L. A.
通讯作者：
Temesvari, L. A.