Receptor-mediated endocytosis in an apicomplexan parasite (Toxoplasma gondii)

Receptor-mediated endocytosis in an apicomplexan parasite (Toxoplasma gondii)
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DOI:
10.1006/expr.2001.4624
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发表时间:
2001-07-01
影响因子:
2.1
通讯作者:
Wahlgren, M
Wahlgren, M
中科院分区:
医学4区
文献类型:
--
作者:
Botero-Kleiven, S;Fernández, V;Wahlgren, M

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顶复门寄生虫的内吞作用机制知之甚少。在这里,我们发现弓形虫的细胞外速殖子以特定的、可饱和的方式结合并内化肝素样硫酸化聚糖。聚糖的离散结合发生在速殖子的前三分之一处,在那里它迅速集中在单个管状囊泡隔室中,随着时间的推移,该隔室变得多个。该化合物在细胞内保留数小时,没有明显的胞吐作用或酸化。在异硫氰酸荧光素共轭肝素持续存在的情况下进行孵育可增强活速殖子对这种 li.-and 的结合和内化。两种速殖子表面多肽对肝素表现出很强的结合力和特异性,使它们成为候选受体。液相内吞示踪剂的摄取通过寄生虫细胞同一区域的非特异性胞饮作用发生,但效率低得多。这些观察结果表明,细胞外速殖子可以通过受体特异性和液相内吞机制获取分子。了解这些过程与弓形虫细胞外和细胞内阶段的生理相关性可能会通过将药物输送到速殖子中来直接靶向寄生虫。 (C) 2001 年学术出版社。
Endocytosis mechanisms are poorly known in apicomplexan parasites. Here, we show that extracellular tachyzoites of Toxoplasma gondii bind and internalize heparin-like sulfated glycans in a specific, saturable manner. Discrete binding of the glycan occurs at the anterior third of the tachyzoite, where it is rapidly concentrated inside single tubulo vesicular compartments that become multiple with time. The compound is held for several hours intracellularly with no apparent exocytosis or acidification. Incubation in the continuous presence of fluorescein isothiocyanate-conjugated heparin enhances the binding and internalization of this li.-and by live tachyzoites. Two tachyzoite surface polypeptides exhibit strong binding and specificity for heparin, making them candidate receptors. Uptake of fluid-phase endocytic tracers occurs via nonspecific pinocytosis in the same region of the parasite cell, but with much lower efficiency. These observations show that extracellular tachyzoites can acquire molecules through both receptor-specific and fluid-phase endocytic mechanisms. Understanding the physiological relevance of these processes for the extracellular and intracellular stages of T gondii may bring about direct targeting of the parasite by drug delivery into the tachyzoites. (C) 2001 Academic Press.