Toxoplasma TgAtg8-TgAtg3 Interaction Primarily Contributes to Apicoplast Inheritance and Parasite Growth in Tachyzoite

doi:10.1128/spectrum.01495-21

科研成果详情

题名	Toxoplasma TgAtg8-TgAtg3 Interaction Primarily Contributes to Apicoplast Inheritance and Parasite Growth in Tachyzoite
作者	Cheng, Linyan 1; Tian, Yuan2; Wang, Yan 2; Wang, Tingting2; Yao, Yinning2; Yu, Helin1; Zheng, Xiaozi3; Wu, Mimi2; Zhao, Wei2; Hua, Qianqian 4; Hu, Xin5; Tan, Feng2
发表日期	2022-02
发表期刊	Microbiology spectrum 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Atg3 Atg8 Atg8-family interacting motif Toxoplasma apicoplast autophagy protein-protein interaction.
其他关键词	AUTOPHAGY ; PROTEIN
摘要	The apicoplast, which harbors key pathways involved in biosynthesis of vital metabolites, is a unique and essential nonphotosynthetic plastid organelle in apicomplexan parasites. Intriguingly, autophagy-related protein 8 (Atg8), a highly conserved eukaryotic protein, can localize to the outermost membrane of the apicoplast and modulate its inheritance in both Toxoplasma and Plasmodium parasites. The Atg8-Atg3 interaction plays a key role in Atg8 lipidation and localization, and our previously work in Toxoplasma has suggested that the core Atg8-family interacting motif (AIM) in TgAtg3, 239FADI242, and the R27 residue of TgAtg8 contribute to TgAtg8-TgAtg3 interaction in vitro. However, little is known about the function of this interaction or its importance in tachyzoite growth in Toxoplasma gondii. Here, we generated two complemented cell lines, TgAtg3F239A/I242A and TgAtg8R27E, based on the TgAtg3 and TgAtg8 conditional knockdown cell lines, respectively. We found that both mutant complemented cell lines were severely affected in terms of tachyzoite growth and displayed delayed death upon conditional knockdown of endogenous TgAtg3 or TgAtg8. Intriguingly, both complemented lines appeared to be defective in TgAtg8 lipidation and apicoplast inheritance. Moreover, we showed that the interaction of TgAtg8 and TgAtg3 is critical for TgAtg8 apicoplast localization. In addition, we found that the TgAtg3F239A/I242A complemented line exhibits an integral mitochondrial network upon ablation of endogenous TgAtg3, which is distinct from TgAtg3-depleted parasites with a fragmented mitochondrial network. Taken together, this work solidifies the contribution of the TgAtg8-TgAtg3 interaction to apicoplast inheritance and the growth of T. gondii tachyzoites. IMPORTANCE Toxoplasma gondiiis a widespread intracellular parasite infecting a variety of warm-blooded animals, including humans. Current frontline treatment of toxoplasmosis suffers many drawbacks, including toxicity, drug resistance, and failure to eradicate tissue cysts, underscoring the need to identify novel drug targets for suppression or treatment of toxoplasmosis. TgAtg8 is thought to serve multiple functions in lipidation and is considered essential to the growth and development of both tachyzoites and bradyzoites. Here, we show that Toxoplasma gondii has adapted a conserved Atg8-Atg3 interaction, required for canonical autophagy in other eukaryotes, to function specifically in apicoplast inheritance. Our finding not only highlights the importance of TgAtg8-TgAtg3 interaction in tachyzoite growth but also suggests that this interaction is a promising drug target for the therapy of toxoplasmosis.
资助项目	National Natural Science Foundation of China[LR17H190001];
出版者	AMER SOC MICROBIOLOGY
出版地	WASHINGTON
ISSN	2165-0497
卷号	10 期号:1 页码:e0149521.
DOI	10.1128/spectrum.01495-21
页数	16
WOS类目	Microbiology
WOS研究方向	Microbiology
WOS记录号	WOS:000766015800083
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	35196797
PMC记录号	PMC8865545
SCOPUSEID	2-s2.0-85125155673
通讯作者地址	[Tan, Feng]Department of Parasitology,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Hu, Xin]School of Medical Laboratory Science and School of Life Science,Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Physiology;Ecology;Immunology and Microbiology (all);Genetics;Microbiology (medical);Cell Biology;Infectious Diseases
引用统计	被引频次：1[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/33789
专题	第一临床医学院（信息与工程学院）、附属第一医院基础医学院（机能实验教学中心）检验医学院（生命科学学院、生物学实验教学中心）基础医学院（机能实验教学中心）_基础医学实验教学中心_形态实验教学中心
通讯作者	Hu, Xin; Tan, Feng
作者单位	1.School of the First Clinical Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Department of Parasitology,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 3.Teaching Center of Morphological Experiment,School of Basic Medical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 4.Clinical Laboratory,Dongyang People's Hospital,Zhejiang,Jinhua,China; 5.School of Medical Laboratory Science and School of Life Science,Wenzhou Medical University,Zhejiang,Wenzhou,China
第一作者单位	温州医科大学
通讯作者单位	基础医学院（机能实验教学中心）; 检验医学院（生命科学学院、生物学实验教学中心）
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Cheng, Linyan,Tian, Yuan,Wang, Yan,et al. Toxoplasma TgAtg8-TgAtg3 Interaction Primarily Contributes to Apicoplast Inheritance and Parasite Growth in Tachyzoite[J]. Microbiology spectrum,2022,10(1):e0149521..
APA	Cheng, Linyan., Tian, Yuan., Wang, Yan., Wang, Tingting., Yao, Yinning., ... & Tan, Feng. (2022). Toxoplasma TgAtg8-TgAtg3 Interaction Primarily Contributes to Apicoplast Inheritance and Parasite Growth in Tachyzoite. Microbiology spectrum, 10(1), e0149521..
MLA	Cheng, Linyan,et al."Toxoplasma TgAtg8-TgAtg3 Interaction Primarily Contributes to Apicoplast Inheritance and Parasite Growth in Tachyzoite".Microbiology spectrum 10.1(2022):e0149521..