Antibodies against MAEBL ligand domains M1 and M2 inhibit sporozoite development in vitro
Antibodies against MAEBL ligand domains M1 and M2 inhibit sporozoite development in vitro
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DOI：
10.1128/iai.72.6.3604-3608.2004
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发表时间：
2004-06-01
影响因子：
3.1
通讯作者：
Adams, JH
中科院分区：
文献类型：
--
作者：
Preiser, P;Rénia, L;Adams, JH
MAEBL是一种1型膜蛋白，与红细胞的分裂子侵入和蚊子唾液腺的孢子子侵入有关。该顶细胞器蛋白在结构上与ebl红细胞结合蛋白（如EBA-175）相似，只是MAEBL的串联配体结构域与部分顶膜抗原1的胞外结构域相似，而不是Duffy结合样结构域。虽然中肠孢子体和唾液腺孢子体形态相似，但唾液腺孢子体在感染唾液腺后会经历一段新的基因表达期，表现出明显的表型差异，对哺乳动物宿主的传染性更强。本项目的目的是确定MAEBL在感染性唾液腺孢子子中的分子形态，以及该配体是否在肝细胞孢子子发育到外红细胞阶段中起作用。我们确定MAEBL在唾液腺孢子体中新表达，其形式与存在于中肠孢子体或存在于红细胞阶段的形式不同。这两个配体结构域（M1和M2）在唾液腺孢子子中作为全长膜形式的一部分表达，而其他阶段仅保留M2配体结构域作为蛋白质膜形式的一部分。针对MAEBL细胞外部分富含半胱氨酸的区域开发的抗血清在体外抑制孢子子向外红细胞形式的发育。这些数据表明，MAEBL在疟原虫生命周期的第三个发育阶段发挥了作用。因此，MAEBL是红细胞前阶段疟疾寄生虫疫苗开发的另一个目标。
MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical organelle protein is structurally similar to the ebl erythrocyte binding proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are similar to part of the extracellular domain of apical membrane antigen 1 and not the Duffy binding-like domain. Although midgut and salivary gland sporozoites are morphologically similar, salivary gland sporozoites undergo a period of new gene expression after infecting the salivary glands, display distinct phenotypic differences, and are more infectious for the mammalian host. The objectives of this project were to determine the molecular form of MAEBL in the infectious salivary gland sporozoites and whether the ligand has a role in the sporozoite development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is newly expressed in salivary gland sporozoites and in a form distinct from what is present in the midgut sporozoites or present in erythrocytic stages. Both ligand domains (M1 and M2) were expressed as part of a full-length membrane form of MAEBL in the salivary gland sporozoites in contrast to the other stages that retain only the M2 ligand domain as part of the membrane form of the protein. Antisera developed against the cysteine-rich regions of the extracellular portion of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro. Together these data indicate that MAEBL has a role in this third developmental stage in the life cycle of the malaria parasite. Thus, MAEBL is another target for pre-erythrocytic-stage vaccine development against malaria parasites.