An Atypical F-Actin Capping Protein Modulates Cytoskeleton Behaviors Crucial for Trichomonas vaginalis Colonization
ABSTRACT Cytoadherence and migration are crucial for pathogens to establish colonization in the host. In contrast to a nonadherent isolate of Trichomonas vaginalis, an adherent one expresses more actin-related machinery proteins with more active flagellate-amoeboid morphogenesis, amoeba migration, a...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2023-08-01
|
| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00596-23 |
| _version_ | 1797741702105006080 |
|---|---|
| author | Kai-Hsuan Wang Jing-Yang Chang Fu-An Li Kuan-Yi Wu Shu-Hao Hsu Yen-Ju Chen Tse-Ling Chu Jessica Lin Hong-Ming Hsu |
| author_facet | Kai-Hsuan Wang Jing-Yang Chang Fu-An Li Kuan-Yi Wu Shu-Hao Hsu Yen-Ju Chen Tse-Ling Chu Jessica Lin Hong-Ming Hsu |
| author_sort | Kai-Hsuan Wang |
| collection | DOAJ |
| description | ABSTRACT Cytoadherence and migration are crucial for pathogens to establish colonization in the host. In contrast to a nonadherent isolate of Trichomonas vaginalis, an adherent one expresses more actin-related machinery proteins with more active flagellate-amoeboid morphogenesis, amoeba migration, and cytoadherence, activities that were abrogated by an actin assembly blocker. By immunoprecipitation coupled with label-free quantitative proteomics, an F-actin capping protein (T. vaginalis F-actin capping protein subunit α [TvFACPα]) was identified from the actin-centric interactome. His-TvFACPα was detected at the barbed end of a growing F-actin filament, which inhibited elongation and possessed atypical activity in binding G-actin in in vitro assays. TvFACPα partially colocalized with F-actin at the parasite pseudopod protrusion and formed a protein complex with α-actin through its C-terminal domain. Meanwhile, TvFACPα overexpression suppressed F-actin polymerization, amoeboid morphogenesis, and cytoadherence in this parasite. Ser2 phosphorylation of TvFACPα enriched in the amoeboid stage of adhered trophozoites was reduced by a casein kinase II (CKII) inhibitor. Site-directed mutagenesis and CKII inhibitor treatment revealed that Ser2 phosphorylation acts as a switching signal to alter TvFACPα actin-binding activity and the consequent actin cytoskeleton behaviors. Through CKII signaling, TvFACPα also controls the conversion of adherent trophozoites from amoeboid migration to the flagellate form with axonemal motility. Together, CKII-dependent Ser2 phosphorylation regulates TvFACPα binding to actin to fine-tune cytoskeleton dynamics and drive crucial behaviors underlying host colonization by T. vaginalis. IMPORTANCE Trichomoniasis is one of the most prevalent nonviral sexually transmitted diseases. T. vaginalis cytoadherence to urogenital epithelium cells is the first step in the colonization of the host. However, studies on the mechanisms of cytoadherence have focused mainly on the role of adhesion molecules, and their effects are limited when analyzed by loss- or gain-of-function assays. This study proposes an extra pathway in which the actin cytoskeleton mediated by a capping protein α-subunit may play roles in parasite morphogenesis, cytoadherence, and motility, which are crucial for colonization. Once the origin of the cytoskeleton dynamics could be manipulated, the consequent activities would be controlled as well. This mechanism may provide new potential therapeutic targets to impair this parasite infection and relieve the increasing impact of drug resistance on clinical and public health. |
| first_indexed | 2024-03-12T14:30:31Z |
| format | Article |
| id | doaj.art-a0845fe6e27543aab897e30daa81f339 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-12T14:30:31Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-a0845fe6e27543aab897e30daa81f3392023-08-17T13:04:15ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-08-0111410.1128/spectrum.00596-23An Atypical F-Actin Capping Protein Modulates Cytoskeleton Behaviors Crucial for Trichomonas vaginalis ColonizationKai-Hsuan Wang0Jing-Yang Chang1Fu-An Li2Kuan-Yi Wu3Shu-Hao Hsu4Yen-Ju Chen5Tse-Ling Chu6Jessica Lin7Hong-Ming Hsu8Department of Tropical Medicine and Parasitology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Tropical Medicine and Parasitology, College of Medicine, National Taiwan University, Taipei, TaiwanThe Proteomic Core, Institute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanDepartment of Tropical Medicine and Parasitology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Tropical Medicine and Parasitology, College of Medicine, National Taiwan University, Taipei, TaiwanTaipei First Girls High School, Taipei, TaiwanTaipei First Girls High School, Taipei, TaiwanDepartment of Tropical Medicine and Parasitology, College of Medicine, National Taiwan University, Taipei, TaiwanABSTRACT Cytoadherence and migration are crucial for pathogens to establish colonization in the host. In contrast to a nonadherent isolate of Trichomonas vaginalis, an adherent one expresses more actin-related machinery proteins with more active flagellate-amoeboid morphogenesis, amoeba migration, and cytoadherence, activities that were abrogated by an actin assembly blocker. By immunoprecipitation coupled with label-free quantitative proteomics, an F-actin capping protein (T. vaginalis F-actin capping protein subunit α [TvFACPα]) was identified from the actin-centric interactome. His-TvFACPα was detected at the barbed end of a growing F-actin filament, which inhibited elongation and possessed atypical activity in binding G-actin in in vitro assays. TvFACPα partially colocalized with F-actin at the parasite pseudopod protrusion and formed a protein complex with α-actin through its C-terminal domain. Meanwhile, TvFACPα overexpression suppressed F-actin polymerization, amoeboid morphogenesis, and cytoadherence in this parasite. Ser2 phosphorylation of TvFACPα enriched in the amoeboid stage of adhered trophozoites was reduced by a casein kinase II (CKII) inhibitor. Site-directed mutagenesis and CKII inhibitor treatment revealed that Ser2 phosphorylation acts as a switching signal to alter TvFACPα actin-binding activity and the consequent actin cytoskeleton behaviors. Through CKII signaling, TvFACPα also controls the conversion of adherent trophozoites from amoeboid migration to the flagellate form with axonemal motility. Together, CKII-dependent Ser2 phosphorylation regulates TvFACPα binding to actin to fine-tune cytoskeleton dynamics and drive crucial behaviors underlying host colonization by T. vaginalis. IMPORTANCE Trichomoniasis is one of the most prevalent nonviral sexually transmitted diseases. T. vaginalis cytoadherence to urogenital epithelium cells is the first step in the colonization of the host. However, studies on the mechanisms of cytoadherence have focused mainly on the role of adhesion molecules, and their effects are limited when analyzed by loss- or gain-of-function assays. This study proposes an extra pathway in which the actin cytoskeleton mediated by a capping protein α-subunit may play roles in parasite morphogenesis, cytoadherence, and motility, which are crucial for colonization. Once the origin of the cytoskeleton dynamics could be manipulated, the consequent activities would be controlled as well. This mechanism may provide new potential therapeutic targets to impair this parasite infection and relieve the increasing impact of drug resistance on clinical and public health.https://journals.asm.org/doi/10.1128/spectrum.00596-23actin capping proteinactin cytoskeletoncytoadherencecolonizationTrichomonas vaginalis |
| spellingShingle | Kai-Hsuan Wang Jing-Yang Chang Fu-An Li Kuan-Yi Wu Shu-Hao Hsu Yen-Ju Chen Tse-Ling Chu Jessica Lin Hong-Ming Hsu An Atypical F-Actin Capping Protein Modulates Cytoskeleton Behaviors Crucial for Trichomonas vaginalis Colonization Microbiology Spectrum actin capping protein actin cytoskeleton cytoadherence colonization Trichomonas vaginalis |
| title | An Atypical F-Actin Capping Protein Modulates Cytoskeleton Behaviors Crucial for Trichomonas vaginalis Colonization |
| title_full | An Atypical F-Actin Capping Protein Modulates Cytoskeleton Behaviors Crucial for Trichomonas vaginalis Colonization |
| title_fullStr | An Atypical F-Actin Capping Protein Modulates Cytoskeleton Behaviors Crucial for Trichomonas vaginalis Colonization |
| title_full_unstemmed | An Atypical F-Actin Capping Protein Modulates Cytoskeleton Behaviors Crucial for Trichomonas vaginalis Colonization |
| title_short | An Atypical F-Actin Capping Protein Modulates Cytoskeleton Behaviors Crucial for Trichomonas vaginalis Colonization |
| title_sort | atypical f actin capping protein modulates cytoskeleton behaviors crucial for trichomonas vaginalis colonization |
| topic | actin capping protein actin cytoskeleton cytoadherence colonization Trichomonas vaginalis |
| url | https://journals.asm.org/doi/10.1128/spectrum.00596-23 |
| work_keys_str_mv | AT kaihsuanwang anatypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT jingyangchang anatypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT fuanli anatypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT kuanyiwu anatypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT shuhaohsu anatypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT yenjuchen anatypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT tselingchu anatypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT jessicalin anatypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT hongminghsu anatypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT kaihsuanwang atypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT jingyangchang atypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT fuanli atypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT kuanyiwu atypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT shuhaohsu atypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT yenjuchen atypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT tselingchu atypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT jessicalin atypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization AT hongminghsu atypicalfactincappingproteinmodulatescytoskeletonbehaviorscrucialfortrichomonasvaginaliscolonization |