Eukaryotic Gene Expression Laboratory, National Institute of Immunology, New Delhi, India.
PLoS One. 2012;7(4):e35855. doi: 10.1371/journal.pone.0035855. Epub 2012 Apr 27.
The actomyosin motor complex of the glideosome provides the force needed by apicomplexan parasites such as Toxoplasma gondii (Tg) and Plasmodium falciparum (Pf) to invade their host cells and for gliding motility of their motile forms. Glideosome Associated Protein 45 (PfGAP45) is an essential component of the glideosome complex as it facilitates anchoring and effective functioning of the motor. Dissection of events that regulate PfGAP45 may provide insights into how the motor and the glideosome operate. We found that PfGAP45 is phosphorylated in response to Phospholipase C (PLC) and calcium signaling. It is phosphorylated by P. falciparum kinases Protein Kinase B (PfPKB) and Calcium Dependent Protein Kinase 1 (PfCDPK1), which are calcium dependent enzymes, at S89, S103 and S149. The Phospholipase C pathway influenced the phosphorylation of S103 and S149. The phosphorylation of PfGAP45 at these sites is differentially regulated during parasite development. The localization of PfGAP45 and its association may be independent of the phosphorylation of these sites. PfGAP45 regulation in response to calcium fits in well with the previously described role of calcium in host cell invasion by malaria parasite.
滑行体的肌动球蛋白马达复合物为刚地弓形虫（Tg）和恶性疟原虫（Pf）等顶复门寄生虫提供了入侵宿主细胞所需的力，并为其运动形式的滑行运动提供了动力。滑行体相关蛋白 45（PfGAP45）是滑行体复合物的必需组成部分，因为它有助于锚定和有效发挥马达的功能。对调节 PfGAP45 的事件进行剖析，可能有助于了解马达和滑行体的工作原理。我们发现 PfGAP45 可响应磷脂酶 C（PLC）和钙信号而发生磷酸化。PfGAP45 可被 PfPKB 和 PfCDPK1（钙依赖性酶）磷酸化，磷酸化位点为 S89、S103 和 S149。PLC 途径影响 S103 和 S149 的磷酸化。PfGAP45 在这些位点的磷酸化在寄生虫发育过程中受到差异调控。PfGAP45 的定位及其与其他蛋白的关联可能独立于这些位点的磷酸化。钙对 PfGAP45 的调节与先前描述的钙在疟原虫入侵宿主细胞中的作用非常吻合。
