Potential role of a CD36-like class B scavenger receptor in the binding of modified low-density lipoprotein (acLDL) to the tegumental surface of Schistosoma mansoni sporocysts
Potential role of a CD36-like class B scavenger receptor in the binding of modified low-density lipoprotein (acLDL) to the tegumental surface of Schistosoma mansoni sporocysts
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DOI：
10.1016/j.molbiopara.2005.12.010
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发表时间：
2006-04-01
影响因子：
1.5
通讯作者：
Yoshino, TP
中科院分区：
文献类型：
--
作者：
Dinguirard, N;Yoshino, TP
先前的研究已经记录了低密度脂蛋白（LDL）与人类血吸虫曼氏血吸虫哺乳动物阶段的皮膜表面的结合，并且这种结合可能在获取宿主脂质以用于营养和/或免疫逃避目的中发挥作用。为了确定曼氏沙门氏菌的软体动物母孢子被阶段是否也具有获得外源 LDL 的能力，用 DiI 标记的 LDL (LDL-DiI) 或乙酰化 LDL (acLDL-DiI) 处理通过体外转化分离的毛蚴获得的活孢子被。孢子被的结合显着不同，在外皮表面表现出与 acLDL-DiI 的强标记，而与 LDL-DiI 的结合较弱。由于已知清道夫受体 (SR) 选择性结合修饰（乙酰化或氧化）的 LDL 和其他聚阴离子分子，因此在 acLDL-DiI 结合抑制测定中使用了已知 SR 的各种潜在配体。观察到岩藻依聚糖、聚肌苷酸和硫酸葡聚糖具有显着的 acLDL-DiI 结合抑制作用，但聚胞苷酸和葡聚糖则没有，这种结合抑制模式与 SR A 或 C 类活性一致。从曼氏链霉菌 EST 序列中，我们从孢子囊 cDNA 中克隆了清道夫受体同源物，其编码的蛋白质与属于 CD36 超家族的 SR B 类 (SRB) 分子具有 31% 的氨基酸序列同一性和 50% 的相似性。使用 RNA 干扰测定，用曼氏沙门氏菌 SRB 基因的 517 bp 双链 RNA 处理毛蚴，在 dsRNA 暴露 6 天后，导致孢子囊中 SRB 转录水平显着且特异性的敲低 (60-70%)，并且与 dsRNA 孵育后 8 和 10 天时 acLDL-DII 与孢子囊的结合显着减少相关。 dsRNA 处理后孢子被长度也出现时间依赖性减少。使用RNA干扰（RNAi）将acLDL与克隆的SRB样曼氏葡萄球菌基因结合的功能性联系表明，皮层SRB样蛋白作为修饰LDL的受体可能发挥作用。孢子被生长的抑制也表明该 SR 同源物可能参与幼虫生长和/或发育的某些方面。 (c) 2006 Elsevier B.V. 保留所有权利。
Previous studies have documented the binding of low density lipoproteins (LDLs) to the tegumental surface of the mammalian stage of the human blood fluke Schistosoma mansoni, and that such binding may be functioning in the acquisition of host lipids for nutritional and/or immune evasion purposes. To determine if the intramolluscan mother sporocyst stage of S. mansoni also possess the ability to acquire exogenous LDL, live sporocysts, derived by in vitro transformation of isolated miracidia, were treated with DiI-labeled LDL (LDL-DiI) or acetylated LDL (acLDL-DiI). Sporocysts markedly differed in their binding, exhibiting strong labeling at the tegumental surface with acLDL-DiI, and only weak binding of LDL-DiI. As scavenger receptors (SRs) are known to selectively bind modified (acetylated or oxidized) LDL and other polyanionic molecules, various potential ligands of known SRs were used in an acLDL-DiI binding inhibition assay. Significant acLDL-DiI binding inhibition was observed for fucoidan, polyinosinic acid and dextran sulfate, but not for polycytidylic acid and dextran, a binding inhibition pattern consistent with SR class A or C activity. From a S. mansoni EST sequence, we cloned a scavenger receptor homologue from sporocyst cDNA that encoded a protein with 31% amino acid sequence identity and 50% similarity to a SR class B (SRB) molecule, belonging to the CD36 superfamily. Using an RNA interference assay, treatment of miracidia with a 517 bp double-stranded RNA of the S. mansoni SRB gene resulted in a significant and specific knockdown (60-70%) of SRB transcript levels in sporocysts after 6 days of dsRNA exposure and was associated with a significant reduction in acLDL-DiI binding to sporocysts at 8 and 10 days post-dsRNA incubation. There also was a time-dependent decrease in sporocyst length following dsRNA treatments. The functional linkage of acLDL binding to the cloned SRB-like S. mansoni gene using RNA interference (RNAi) suggests a possible role of the tegumental SRB-like protein as a receptor for modified LDL. Inhibition of sporocyst growth also indicates a potential involvement of this SR homologue in some aspect of larval growth and/or development. (c) 2006 Elsevier B.V. All rights reserved.