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红细胞信号传导在侵袭过程中功能保守。

Red blood cell signaling is functionally conserved in invasion.

作者信息

Yong James Jia Ming, Gao Xiaohong, Prakash Prem, Ang Jing Wen, Lai Soak Kuan, Chen Ming Wei, Neo Jason Jun Long, Lescar Julien, Li Hoi Yeung, Preiser Peter R

机构信息

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.

出版信息

iScience. 2024 Sep 26;27(10):111052. doi: 10.1016/j.isci.2024.111052. eCollection 2024 Oct 18.

DOI:10.1016/j.isci.2024.111052
PMID:39635131
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11615254/
Abstract

It is widely recognized that merozoites secrete ligands that interact with RBC receptors. Meanwhile the question on whether these interactions trigger RBC signals essential for invasion remains unresolved. There is evidence that parasites manipulate native RBC Ca signaling to facilitate invasion. Here, we demonstrate a key role of RBC Ca influx that is conserved across different species during invasion. RH5-basigin interaction triggers RBC cAMP increase to promote Ca influx. The RBC signaling pathways can be blocked by a range of inhibitors during invasion, providing the evidence of a functionally conserved host cAMP-Ca signaling that drives invasion and junction formation. Furthermore, RH5-basigin binding induces a pre-existing multimeric RBC membrane complex to undergo increased protein association containing the cAMP-inducing β-adrenergic receptor. Our work presents evidence of a conserved host cell signaling cascade necessary for invasion and will create opportunities to therapeutically target merozoite invasion.

摘要

普遍认为,裂殖子分泌与红细胞(RBC)受体相互作用的配体。与此同时,这些相互作用是否触发入侵所必需的红细胞信号这一问题仍未得到解决。有证据表明,寄生虫操纵天然红细胞的钙信号以促进入侵。在此,我们证明了红细胞钙内流在不同物种入侵过程中的关键作用,该作用具有保守性。RH5-基底结合素相互作用触发红细胞环磷酸腺苷(cAMP)增加以促进钙内流。在入侵过程中,一系列抑制剂可阻断红细胞信号通路,这为驱动入侵和连接形成的功能保守的宿主cAMP-钙信号提供了证据。此外,RH5-基底结合素结合诱导预先存在的多聚红细胞膜复合物增加蛋白质结合,其中包含诱导cAMP的β-肾上腺素能受体。我们的工作为入侵所必需的保守宿主细胞信号级联提供了证据,并将为治疗性靶向裂殖子入侵创造机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/3ae4d668d76c/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/c57d4ab3fe13/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/e2544165dbef/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/19a2f435d1ef/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/12912c7ad828/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/09325db4a424/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/5fb522fd8729/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/c6062db0266d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/b1856179b567/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/3ae4d668d76c/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/c57d4ab3fe13/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/e2544165dbef/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/19a2f435d1ef/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/12912c7ad828/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/09325db4a424/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/5fb522fd8729/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/c6062db0266d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/b1856179b567/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f093/11615254/3ae4d668d76c/gr8.jpg

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本文引用的文献

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Proteomic Analysis of the Role of the Adenylyl Cyclase-cAMP Pathway in Red Blood Cell Mechanical Responses.蛋白质组学分析腺苷酸环化酶-cAMP 通路在红细胞机械反应中的作用。
Cells. 2022 Apr 6;11(7):1250. doi: 10.3390/cells11071250.
2
Gliding motility of merozoites.裂殖子的滑行运动。
Proc Natl Acad Sci U S A. 2021 Nov 30;118(48). doi: 10.1073/pnas.2114442118.
3
Zoonotic Malaria: Non- Biology and Invasion Mechanisms.人畜共患疟疾:非生物学及入侵机制
Pathogens. 2021 Jul 13;10(7):889. doi: 10.3390/pathogens10070889.
4
Erythrocyte Binding Like Protein Interacts With Basigin, an Erythrocyte Surface Protein.红细胞结合样蛋白与红细胞表面蛋白基底素相互作用。
Front Cell Infect Microbiol. 2021 Apr 14;11:656620. doi: 10.3389/fcimb.2021.656620. eCollection 2021.
5
Basigin drives intracellular accumulation of l-lactate by harvesting protons and substrate anions.Basigin 通过收集质子和底物阴离子来驱动 l-乳酸的细胞内积累。
PLoS One. 2021 Mar 26;16(3):e0249110. doi: 10.1371/journal.pone.0249110. eCollection 2021.
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Subcellular Organization of the cAMP Signaling Pathway.细胞信号转导途径 cAMP 的亚细胞结构。
Pharmacol Rev. 2021 Jan;73(1):278-309. doi: 10.1124/pharmrev.120.000086.
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Characterization of the erythrocyte GTPase Rac1 in relation to Plasmodium falciparum invasion.红细胞 GTPase Rac1 的特性与恶性疟原虫入侵的关系。
Sci Rep. 2020 Dec 16;10(1):22054. doi: 10.1038/s41598-020-79052-0.
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Signal Transduct Target Ther. 2020 Dec 4;5(1):283. doi: 10.1038/s41392-020-00426-x.
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cAMP signalling and its role in host cell invasion by malaria parasites.cAMP 信号转导及其在疟原虫感染宿主细胞中的作用。
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