Structural organization of erythrocyte membrane microdomains and their relation with malaria susceptibility.

Structural organization of erythrocyte membrane microdomains and their relation with malaria susceptibility.
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DOI:
10.1038/s42003-021-02900-w
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发表时间:
2021-12-08
影响因子:
5.9
通讯作者:
Ponzi M
Ponzi M
中科院分区:
生物学2区
文献类型:
--
作者:
Olivieri A;Lee RS;Fratini F;Keutcha C;Chaand M;Mangano V;Celani F;Mochi S;Birago C;Paone S;Grasso F;Tirelli V;Falchi M;Shabani E;Bertoncini S;Sirima BS;Pizzi E;Modiano D;Duraisingh MT;Ponzi M

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富含胆固醇的微结构域是以特定的脂质和蛋白质组成为特征的膜室。这些动态组合参与了几个生物过程,包括细胞内病原体的感染。这项工作提供了一个全面的分析组成的人红细胞膜微域。基于它们的漂浮特性,我们还将微结构域相关蛋白分类为簇。有趣的是,红细胞微结构域包括绝大多数已知参与疟疾寄生虫恶性疟原虫入侵的蛋白质。我们在这里发现,在一个特定的簇中发现的ecto - adp -核糖基转移酶4 (ART4)和水通道蛋白1 (AQP1),包含必需的宿主决定因子CD55,被招募到寄生虫进入的部位,然后内化到新形成的寄生物液泡膜中。通过产生无红系细胞系,我们发现其中一种蛋白ART4在恶性疟原虫侵袭中起作用。我们还发现,在疟疾流行人群中,ART4和AQP1的遗传变异与该病的易感性有关。Olivieri等人利用微结构域相关蛋白的漂浮特性来研究恶性疟原虫红细胞侵袭的重要宿主蛋白。利用蛋白质组学和生物信息学方法,他们分析了红细胞耐洗剂膜(DRMs)的蛋白质丰度谱簇,并鉴定了一种宿主蛋白ART4,它对恶性疟原虫入侵红细胞很重要。
Cholesterol-rich microdomains are membrane compartments characterized by specific lipid and protein composition. These dynamic assemblies are involved in several biological processes, including infection by intracellular pathogens. This work provides a comprehensive analysis of the composition of human erythrocyte membrane microdomains. Based on their floating properties, we also categorized the microdomain-associated proteins into clusters. Interestingly, erythrocyte microdomains include the vast majority of the proteins known to be involved in invasion by the malaria parasite Plasmodium falciparum. We show here that the Ecto-ADP-ribosyltransferase 4 (ART4) and Aquaporin 1 (AQP1), found within one specific cluster, containing the essential host determinant CD55, are recruited to the site of parasite entry and then internalized to the newly formed parasitophorous vacuole membrane. By generating null erythroid cell lines, we showed that one of these proteins, ART4, plays a role in P. falciparum invasion. We also found that genetic variants in both ART4 and AQP1 are associated with susceptibility to the disease in a malaria-endemic population. Olivieri et al. exploit floating properties of microdomain-associated proteins to investigate host proteins important for Plasmodium falciparum erythrocyte invasion. Using proteomic and bioinformatic approaches, they analyze clusters of protein abundance profiles from detergent resistant membranes (DRMs) of erythrocytes and identify a host protein, ART4, important for P. falciparum invasion into RBCs.
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