Toxoplasma gondii microneme secretion involves intracellular Ca2+ release from inositol 1,4,5-triphosphate (IP3)/ryanodine-sensitive stores.
Toxoplasma gondii microneme secretion involves intracellular Ca2+ release from inositol 1,4,5-triphosphate (IP3)/ryanodine-sensitive stores.
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DOI：
10.1074/jbc.m202553200
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发表时间：
2002-07-19
影响因子：
4.8
通讯作者：
Sibley, LD
中科院分区：
文献类型：
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作者：
Lovett, JL;Marchesini, N;Sibley, LD
弓形虫中钙介导的微线体分泌通过与宿主细胞接触而受到刺激，导致介导附着的粘附素的释放。钙的细胞内来源和触发释放的信号通路尚未被表征，这促使我们寻找弓形虫中钙信号和微线体分泌的介质。我们确定了微线体分泌的两种刺激物，兰尼碱和咖啡因，它们增强了寄生虫细胞内储存的钙的释放。乙醇是一种先前确定的微线体分泌触发剂，可刺激寄生虫肌醇 1,4,5-三磷酸的增加，这意味着该第二信使可能介导细胞内钙的释放。与这一观察结果一致，xestospongin C（一种肌醇 1,4,5-三磷酸受体拮抗剂）抑制微线体分泌并阻止寄生虫附着和入侵宿主细胞。总的来说，这些结果表明弓形虫拥有具有肌醇 1,4,5-三磷酸/兰尼丁受体超家族特性的细胞内钙释放通道。细胞内钙通道以前几乎只在多细胞动物中进行研究，似乎对于寄生虫进入宿主细胞的初始步骤中钙的控制也至关重要。
Calcium-mediated microneme secretion in Toxoplasma gondii is stimulated by contact with host cells, resulting in the discharge of adhesins that mediate attachment. The intracellular source of calcium and the signaling pathway(s) triggering release have not been characterized, prompting our search for mediators of calcium signaling and microneme secretion in T. gondii. We identified two stimuli of microneme secretion, ryanodine and caffeine, which enhanced release of calcium from parasite intracellular stores. Ethanol, a previously characterized trigger of microneme secretion, stimulated an increase in parasite inositol 1,4,5-triphosphate, implying that this second messenger may mediate intracellular calcium release. Consistent with this observation, xestospongin C, an inositol 1,4,5-triphosphate receptor antagonist, inhibited microneme secretion and blocked parasite attachment and invasion of host cells. Collectively, these results suggest that T. gondii possess an intracellular calcium release channel with properties of the inositol 1,4,5-triphosphate/ryanodine receptor superfamily. Intracellular calcium channels, previously studied almost exclusively in multicellular animals, appear to also be critical to the control of parasite calcium during the initial steps of host cell entry.