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一种 C2 结构域蛋白激酶在原生动物寄生虫溶组织内阿米巴中引发吞噬作用。

A C2 domain protein kinase initiates phagocytosis in the protozoan parasite Entamoeba histolytica.

机构信息

School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

出版信息

Nat Commun. 2011;2:230. doi: 10.1038/ncomms1199.

DOI:10.1038/ncomms1199
PMID:21407196
Abstract

Phagocytosis is a process whereby particles are taken in by cells through mechanisms superficially similar to those for endocytosis. It serves a wide range of functions, from providing nutrition in unicellular organisms to initiation of both innate and adaptive immunity in vertebrates. In the protozoan parasite Entamoeba histolytica, it has an essential role in survival and pathogenesis. In this study, we show that EhC2PK, a C2-domain-containing protein kinase, and the Ca²(+) and actin-binding protein, EhCaBP1, are involved in the initiation of phagocytosis in E. histolytica. Conditional suppression of EhC2PK expression and overexpression of a mutant form reveals its role in the initiation of phagocytic cups. EhC2PK binds phosphatidylserine in the presence of Ca²(+) and thereby recruits EhCaBP1 and actin to the membrane. Identification of these proteins in phagocytosis is an important step in amoebic biology and these molecules could be the important targets for developing novel therapies against amoebiasis.

摘要

吞噬作用是细胞通过与胞吞作用表面上相似的机制摄取颗粒的过程。它具有广泛的功能,从为单细胞生物提供营养到启动脊椎动物的先天和适应性免疫。在原生动物寄生虫溶组织内阿米巴中,它在生存和发病机制中起着至关重要的作用。在这项研究中,我们表明,含 C2 结构域的蛋白激酶 EhC2PK 和 Ca²(+)和肌动蛋白结合蛋白 EhCaBP1 参与了溶组织内阿米巴吞噬作用的启动。EhC2PK 表达的条件性抑制和突变体形式的过表达揭示了其在吞噬杯起始中的作用。EhC2PK 在 Ca²(+)存在下结合磷脂酰丝氨酸,从而将 EhCaBP1 和肌动蛋白募集到膜上。这些蛋白在吞噬作用中的鉴定是阿米巴生物学的重要步骤,这些分子可能是开发针对阿米巴病的新型治疗方法的重要靶点。

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本文引用的文献

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Serum-dependent selective expression of EhTMKB1-9, a member of Entamoeba histolytica B1 family of transmembrane kinases.血清依赖性的EhTMKB1-9 的选择性表达,EhTMKB1-9 是溶组织内阿米巴 B1 家族跨膜激酶的一个成员。
PLoS Pathog. 2010 Jun 3;6(6):e1000929. doi: 10.1371/journal.ppat.1000929.
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The role of calcium signaling in phagocytosis.钙信号在吞噬作用中的作用。
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A Cdc42 activation cycle coordinated by PI 3-kinase during Fc receptor-mediated phagocytosis.
PLoS Pathog. 2021 Nov 22;17(11):e1010030. doi: 10.1371/journal.ppat.1010030. eCollection 2021 Nov.
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The Multiple Roles of Trogocytosis in Immunity, the Nervous System, and Development.胞饮作用在免疫、神经系统和发育中的多重作用。
Biomed Res Int. 2021 Sep 22;2021:1601565. doi: 10.1155/2021/1601565. eCollection 2021.
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Revisiting Drug Development Against the Neglected Tropical Disease, Amebiasis.重新审视针对被忽视热带病——阿米巴病的药物研发。
Front Cell Infect Microbiol. 2021 Feb 24;10:628257. doi: 10.3389/fcimb.2020.628257. eCollection 2020.
6
Uncovering the Cyclic AMP Signaling Pathway of the Protozoan Parasite and Understanding Its Role in Phagocytosis.揭示原生动物寄生虫的环腺苷酸信号通路,并了解其在吞噬作用中的作用。
Front Cell Infect Microbiol. 2020 Sep 25;10:566726. doi: 10.3389/fcimb.2020.566726. eCollection 2020.
7
Structural and functional diversity of Entamoeba histolytica calcium-binding proteins.溶组织内阿米巴钙结合蛋白的结构与功能多样性
Biophys Rev. 2020 Oct 15;12(6):1331-41. doi: 10.1007/s12551-020-00766-6.
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Rab7D small GTPase is involved in phago-, trogocytosis and cytoskeletal reorganization in the enteric protozoan Entamoeba histolytica.Rab7D 小分子 GTPase 参与了肠道原生动物溶组织内阿米巴的吞噬作用、胞饮作用和细胞骨架重排。
Cell Microbiol. 2021 Jan;23(1):e13267. doi: 10.1111/cmi.13267. Epub 2020 Nov 1.
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10
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8
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Cell Microbiol. 2008 Jun;10(6):1373-89. doi: 10.1111/j.1462-5822.2008.01134.x. Epub 2008 Mar 11.
9
Entamoeba histolytica phagocytosis of human erythrocytes involves PATMK, a member of the transmembrane kinase family.溶组织内阿米巴对人类红细胞的吞噬作用涉及跨膜激酶家族成员PATMK。
PLoS Pathog. 2008 Jan;4(1):e8. doi: 10.1371/journal.ppat.0040008.
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EhGEF3, a novel Dbl family member, regulates EhRacA activation during chemotaxis and capping in Entamoeba histolytica.EhGEF3是一种新型的Dbl家族成员,在溶组织内阿米巴的趋化性和帽化过程中调节EhRacA的激活。
Cell Motil Cytoskeleton. 2007 May;64(5):390-404. doi: 10.1002/cm.20191.