Role in host cell invasion of Trypanosoma cruzi-induced cytosolic-free Ca2+ transients.
Role in host cell invasion of Trypanosoma cruzi-induced cytosolic-free Ca2+ transients.
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DOI：
10.1084/jem.179.3.1017
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发表时间：
1994-03-01
期刊：
影响因子：
--
通讯作者：
Andrews NW
中科院分区：
文献类型：
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作者：
Tardieux I;Nathanson MH;Andrews NW
克氏锥虫通过一种独特的机制进入细胞，与吞噬作用不同。侵袭是通过破坏宿主细胞肌动蛋白微丝而促进的，并涉及宿主溶酶体在寄生虫进入部位的招募和融合。这些发现表明，在寄生虫入侵之前，宿主细胞中存在由寄生虫触发的跨膜信号机制。在这里，我们发现感染的锥虫或其分离的膜，而不是非感染的上胚体，以百日咳毒素敏感的方式在单个正常大鼠肾成纤维细胞中诱导重复的胞浆游离钙瞬变。通过缓冲或耗尽寄主细胞内游离的钙离子，或者用钙离子通道阻滞剂或百日咳毒素进行预处理，寄生虫的进入被抑制。相反，宿主细胞短暂暴露于细胞松弛素D后，侵袭能力增强。这些结果表明，类鞭毛体膜因子通过G蛋白偶联途径在宿主细胞内触发胞浆内游离钙离子瞬变。这一信号事件可能通过调节宿主细胞的肌动蛋白细胞骨架来促进侵袭。
Trypanosoma cruzi enters cells by a unique mechanism, distinct from phagocytosis. Invasion is facilitated by disruption of host cell actin microfilaments, and involves recruitment and fusion of host lysosomes at the site of parasite entry. These findings implied the existence of transmembrane signaling mechanisms triggered by the parasites in the host cells before invasion. Here we show that infective trypomastigotes or their isolated membranes, but not the noninfective epimastigotes, induce repetitive cytosolic-free Ca2+ transients in individual normal rat kidney fibroblasts, in a pertussis toxin-sensitive manner. Parasite entry is inhibited by buffering or depleting host cell cytosolic-free Ca2+, or by pretreatment with Ca2+ channel blockers or pertussis toxin. In contrast, invasion is enhanced by brief exposure of the host cells to cytochalasin D. These results indicate that a trypomastigote membrane factor triggers cytosolic-free Ca2+ transients in host cells through a G-protein-coupled pathway. This signaling event may promote invasion through modulation of the host cell actin cytoskeleton.