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- Title
PIP<sub>2</sub> regulating calcium signal modulates actin cytoskeleton-dependent cytoadherence and cytolytic capacity in the protozoan parasite Trichomonas vaginalis.
- Authors
Chen, Yen-Ju; Wu, Kuan-Yi; Lin, Shu-Fan; Huang, Sung-Hsi; Hsu, Heng-Cheng; Hsu, Hong-Ming
- Abstract
Trichomonas vaginalis is a prevalent causative agent that causes trichomoniasis leading to uropathogenic inflammation in the host. The crucial role of the actin cytoskeleton in T. vaginalis cytoadherence has been established but the associated signaling has not been fully elucidated. The present study revealed that the T. vaginalis second messenger PIP2 is located in the recurrent flagellum of the less adherent isolate and is more abundant around the cell membrane of the adherent isolates. The T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) with conserved activity phosphorylating PI(4)P to PI(4, 5)P2 was highly expressed in the adherent isolate and partially colocalized with PIP2 on the plasma membrane but with discrete punctate signals in the cytoplasm. Plasma membrane PIP2 degradation by phospholipase C (PLC)-dependent pathway concomitant with increasing intracellular calcium during flagellate-amoeboid morphogenesis. This could be inhibited by Edelfosine or BAPTA simultaneously repressing parasite actin assembly, morphogenesis, and cytoadherence with inhibitory effects similar to the iron-depleted parasite, supporting the significance of PIP2 and iron in T. vaginalis colonization. Intriguingly, iron is required for the optimal expression and cell membrane trafficking of TvPI4P5K for in situ PIP2 production, which was diminished in the iron-depleted parasites. TvPI4P5K-mediated PIP2 signaling may coordinate with iron to modulate T. vaginalis contact-dependent cytolysis to influence host cell viability. These observations provide novel insights into T. vaginalis cytopathogenesis during the host-parasite interaction. Author summary: Signal transduction in T. vaginalis pathogenesis remains elusive despite elucidation of the distinctive actin-based cytoadherence of the adherent isolates. Herein, we identified a T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) which converts PI(4)P into PI(4, 5)P2. Differential TvPI4P5K expression and specific PIP2 localization in the T. vaginalis isolates with distinct cytoadherence suggest a potential link underlying PIP2 signaling and cytoskeleton behaviors in this parasite. In the parasite transforming from the flagellate into an amoeboid trophozoite, the plasma membrane PIP2 signal may be cleaved by a phospholipase C (PLC)-like pathway, thereafter increasing intracellular calcium, both of which are required for parasite actin assembly, morphogenesis, and cytoadherence. Moreover, environmental iron elicited TvPI4P5K and PIP2 expression and triggered TvPI4P5K translocation to the plasma membrane. PIP2 signaling also modulated the extracellular cytopathic effectors from the parasite to lyse host cells. Our study reveals the biological significance of PIP2 signal transduction in regulating T. vaginalis pathogenesis, which may be a potential therapeutic target.
- Subjects
TRICHOMONAS vaginalis; CYTOSKELETON; INTRACELLULAR calcium; PHOSPHOLIPASE C; ACTIN; CELL membranes; IRON; URODYNAMICS; PLANT translocation
- Publication
PLoS Pathogens, 2023, Vol 19, Issue 12, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1011891