The protozoan parasite Plasmodium falciparum, which is responsible for the deadliest form of human malaria, accounts for over half a million deaths a year. These parasites proliferate in human red blood cells by consecutive rounds of closed mitoses called schizogony. Their virulence is attributed to their ability to modify the infected red cells to adhere to the vascular endothelium and to evade immunity through antigenic switches. Spatial dynamics at the nuclear periphery were associated with regulation of processes that enable the parasites to establish long-term infection. However, our knowledge of components of the nuclear envelope (NE) in Plasmodium remains limited. One of the major protein complexes at the NE is the LINC complex that forms a connecting bridge between the cytoplasm and the nucleus through the interaction of SUN and KASH domain proteins. Here we have identified two SUN-domain proteins as components of the LINC complex of P. falciparum and show that their proper expression is essential for the parasite’s proliferation in human red blood cells and that their depletion leads to the formation of membranous whorls and morphological changes of the NE. In addition, we found that PfSUN2 is associated with heterochromatin and that PfSUN1 expression is essential for activation of the DNA damage response. Our data provide indications for the involvement of the LINC complex in crucial biological processes in the intraerythrocytic development cycle of malaria parasites.

中文翻译：

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疟原虫恶性疟原虫的 SUN 结构域蛋白对于正确的核分裂和 DNA 修复至关重要

原生动物寄生虫恶性疟原虫是最致命的人类疟疾的罪魁祸首，每年导致超过 50 万人死亡。这些寄生虫通过连续轮次的闭合有丝分裂（称为分裂生殖）在人类红细胞中增殖。它们的毒力归因于它们能够改变受感染的红细胞，使其粘附在血管内皮上，并通过抗原开关逃避免疫。核外围的空间动力学与寄生虫能够建立长期感染的过程的调节有关。然而，我们对疟原虫核膜（NE）成分的了解仍然有限。 NE 的主要蛋白质复合物之一是 LINC 复合物，它通过 SUN 和 KASH 结构域蛋白的相互作用在细胞质和细胞核之间形成连接桥梁。在这里，我们鉴定了两种 SUN 结构域蛋白作为恶性疟原虫 LINC 复合物的组成部分，并表明它们的正确表达对于寄生虫在人红细胞中的增殖至关重要，并且它们的消耗导致膜轮的形成和形态变化NE 的。此外，我们发现 PfSUN2 与异染色质相关，并且 PfSUN1 的表达对于激活 DNA 损伤反应至关重要。我们的数据表明 LINC 复合物参与疟原虫红细胞内发育周期的关键生物过程。