Pace Douglas A, McKnight Ciara A, Liu Jing, Jimenez Veronica, Moreno Silvia N J
From the Center for Tropical and Emerging Global Diseases and.
From the Center for Tropical and Emerging Global Diseases and the Department of Cellular Biology, University of Georgia, Athens, Georgia 30602 and.
J Biol Chem. 2014 Jul 11;289(28):19637-47. doi: 10.1074/jbc.M114.565390. Epub 2014 May 27.
During invasion and egress from their host cells, Apicomplexan parasites face sharp changes in the surrounding calcium ion (Ca(2+)) concentration. Our work with Toxoplasma gondii provides evidence for Ca(2+) influx from the extracellular milieu leading to cytosolic Ca(2+) increase and enhancement of virulence traits, such as gliding motility, conoid extrusion, microneme secretion, and host cell invasion. Assays of Mn(2+) and Ba(2+) uptake do not support a canonical store-regulated Ca(2+) entry mechanism. Ca(2+) entry was blocked by the L-type Ca(2+) channel inhibitor nifedipine and stimulated by the increase in cytosolic Ca(2+) and by the specific L-type Ca(2+) channel agonist Bay K-8644. Our results demonstrate that Ca(2+) entry is critical for parasite virulence. We propose a regulated Ca(2+) entry mechanism activated by cytosolic Ca(2+) that has an enhancing effect on invasion-linked traits.
在侵入宿主细胞和从宿主细胞逸出的过程中，顶复门寄生虫面临周围钙离子（Ca(2+)）浓度的急剧变化。我们对刚地弓形虫的研究工作为细胞外环境中的Ca(2+)内流提供了证据，这种内流导致胞质Ca(2+)增加，并增强了毒力特征，如滑行运动、类锥体挤出、微线体分泌和宿主细胞入侵。对Mn(2+)和Ba(2+)摄取的测定不支持典型的储存调节性Ca(2+)进入机制。Ca(2+)进入被L型Ca(2+)通道抑制剂硝苯地平阻断，并受到胞质Ca(2+)增加和特定L型Ca(2+)通道激动剂Bay K-8644的刺激。我们的结果表明，Ca(2+)进入对寄生虫毒力至关重要。我们提出了一种由胞质Ca(2+)激活的调节性Ca(2+)进入机制，该机制对与入侵相关的特征具有增强作用。
