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首页> 外文期刊>Current Biology: CB >ISP1-Anchored Polarization of GCβ/CDC50A Complex Initiates Malaria Ookinete Gliding Motility
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ISP1-Anchored Polarization of GCβ/CDC50A Complex Initiates Malaria Ookinete Gliding Motility

机译：isp1锚定极化gcβ/ cdc50a复合物启动疟疾奥克里省滑翔运动

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摘要

Ookinete gliding motility is essential for penetration of the mosquito midgut wall and transmission of malaria parasites. Cyclic guanosine monophosphate (cGMP) signaling has been implicated in ookinete gliding. However, the upstream mechanism of how the parasites activate cGMP signaling and thus initiate ookinete gliding remains unknown. Using real-time imaging to visualizePlasmodium yoeliiguanylate cyclase β (GCβ), we show that cytoplasmic GCβ translocates and polarizes to the parasite plasma membrane at “ookinete extrados site” (OES) during zygote-to-ookinete differentiation. The polarization of enzymatic active GCβ at OES initiates gliding of matured ookinete. Both the P4-ATPase-like domain and guanylate cyclase domain are required for GCβ polarization and ookinete gliding. CDC50A, a co-factor of P4-ATPase, binds to and stabilizes GCβ during ookinete development. Screening of inner membrane complex proteins identifies ISP1 as a key molecule that anchors GCβ/CDC50A complex at the OES of mature ookinetes. This study defines a spatial-temporal mechanism for the initiation of ookinete gliding, where GCβ polarization likely elevates local cGMP levels and activates cGMP-dependent protein kinase signaling.
机译：奥克金蒂滑翔动力对于蚊子壁墙的渗透至关重要，以及疟疾寄生虫的传播。环磷酸循环鸟嘌呤（CGMP）信号传导涉及奥克金特滑动。然而，寄生虫如何激活CGMP信号的上游机制，从而发起霍金特滑翔仍然未知。利用实时成像到VisualizedPraModium yoeliiguantylyly环酶β（GCβ），我们表明细胞质GCβ在比特特 - 霍金特分化期间在“奥努蒂extrados位点”（OES）中的寄生虫浆膜转化和极化。 OES酶活性GCβ的偏振引发了令人恢复的令吉的滑翔。 GCβ偏振和霍灰酱滑动需要P4-ATP酶样结构域和胍基环酶结构域。 CDC50A，P4-ATP酶的共聚因子，结合在霍伊斯特发育过程中与GCβ稳定。内膜复合蛋白的筛选将ISP1鉴定为锚固在成熟oOkinet的OES处的GCβ/ CDC50A复合物的关键分子。该研究定义了用于启动霍绿仔滑翔的空间 - 时间机制，其中GCβ极化可能升高局部CGMP水平并激活CGMP依赖性蛋白激酶信号传导。

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  • 来源
    《Current Biology: CB》 |2018年第17期|共20页
  • 作者

    Han Gao; Zhenke Yang; Xu Wang; Pengge Qian; Renjie Hong; Xin Chen; Xin-zhuan Su; Huiting Cui; Jing Yuan;

  • 作者单位

    State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signal Network School of Life Sciences Xiamen University Xiamen;

    State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signal Network School of Life Sciences Xiamen University Xiamen;

    State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signal Network School of Life Sciences Xiamen University Xiamen;

    State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signal Network School of Life Sciences Xiamen University Xiamen;

    State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signal Network School of Life Sciences Xiamen University Xiamen;

    State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signal Network School of Life Sciences Xiamen University Xiamen;

    Laboratory of Malaria and Vector Research National Institute of Allergy and Infectious Diseases NIH;

    State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signal Network School of Life Sciences Xiamen University Xiamen;

    State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Signal Network School of Life Sciences Xiamen University Xiamen;

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  • 中图分类 生物科学;
  • 关键词

    malaria; Plasmodium; mosquito; ookinete; motility; guanylate cyclase; cGMP; signal transduction;

    机译：疟疾;疟原虫;蚊子;奥克金特;运动;胍基环酶;CGMP;信号转导;

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