Kwecka Dominika, Wang Zhishuo, Eigminas Edvardas, Liu Lijia, Regan Jennifer C, Kim Choel, Philip Nisha
Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
Institute of Molecular Plant Sciences, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
PLoS Pathog. 2025 Sep 2;21(9):e1013467. doi: 10.1371/journal.ppat.1013467. eCollection 2025 Sep.
Colonisation of mosquitos by the malarial parasite is critically reliant on the invasive ookinete stage. Ookinete invasion of mosquito is coordinated by the apical complex, a specialised parasite structure containing components for secretion, attachment and penetration. While studies have investigated cytoskeletal and secretory elements, it is currently unknown if signalling modules are present or functional at the apical complex. Here we elucidate the role of a cryptic cyclic nucleotide-binding protein which we name CBP-O. PbCBP-O showed a marked localisation to the ookinete apex and disruption of the protein severely compromised ookinete invasion of mosquitos. Domain dissection analysis revealed that the N- and C-termini have distinct functions. Intriguingly, PbCBP-O exhibits dual binding specificity to both cGMP and cAMP. Our findings suggest the apical tip of the ookinete is a platform to transduce cyclic nucleotide signals essential for malaria parasite transmission.
疟原虫在蚊子体内的定殖严重依赖于侵入性动合子阶段。动合子对蚊子的侵入由顶复合体协调，顶复合体是一种特殊的寄生虫结构，包含用于分泌、附着和穿透的成分。虽然已有研究调查了细胞骨架和分泌元件，但目前尚不清楚信号模块是否存在于顶复合体中或在顶复合体中发挥作用。在这里，我们阐明了一种神秘的环核苷酸结合蛋白的作用，我们将其命名为CBP-O。PbCBP-O在动合子顶端有明显定位，该蛋白的破坏严重损害了动合子对蚊子的侵入。结构域剖析分析表明，N端和C端具有不同的功能。有趣的是，PbCBP-O对cGMP和cAMP都表现出双重结合特异性。我们的研究结果表明，动合子的顶端是一个转导疟原虫传播所必需的环核苷酸信号的平台。
