Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115.
Division of Infectious Diseases, Boston Children's Hospital, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2204167119. doi: 10.1073/pnas.2204167119. Epub 2022 Aug 16.
Malaria remains a global driver of morbidity and mortality. To generate new antimalarials, one must elucidate the fundamental cell biology of , the parasite responsible for the deadliest cases of malaria. A membranous and proteinaceous scaffold called the inner membrane complex (IMC) supports the parasite during morphological changes, including segmentation of daughter cells during asexual replication and formation of transmission-stage gametocytes. The basal complex lines the edge of the IMC during segmentation and likely facilitates IMC expansion. It is unknown, however, what drives IMC expansion during gametocytogenesis. We describe the discovery of a basal complex protein, PfBLEB, which we find to be essential for gametocytogenesis. Parasites lacking PfBLEB harbor defects in IMC expansion and are unable to form mature gametocytes. This article demonstrates a role for a basal complex protein outside of asexual division, and, importantly, highlights a potential molecular target for the ablation of malaria transmission.
疟疾仍然是全球发病率和死亡率的主要驱动因素。为了开发新的抗疟药物，人们必须阐明寄生虫的基本细胞生物学，寄生虫是导致疟疾最致命病例的罪魁祸首。一种叫做内膜复合物（IMC）的膜状和蛋白质支架在形态发生变化期间为寄生虫提供支持，包括无性复制期间子细胞的分割和传播阶段配子体的形成。基础复合物在分割期间位于 IMC 的边缘，并可能促进 IMC 的扩张。然而，在配子体发生过程中是什么驱动 IMC 的扩张尚不清楚。我们描述了内膜复合物蛋白 PfBLEB 的发现，我们发现它对配子体发生至关重要。缺乏 PfBLEB 的寄生虫在 IMC 扩张中存在缺陷，并且无法形成成熟的配子体。本文证明了基础复合物蛋白在无性分裂之外的作用，重要的是，它突出了疟疾传播的潜在分子靶标。
