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Genetic Manipulation in Δku80 Strains for Functional Genomic Analysis of Toxoplasma gondii
Published on: July 12, 2013
ARF6, PI3-kinase and host cell actin cytoskeleton in Toxoplasma gondii cell invasion
Claudio Vieira da Silva1, Erika Alves da Silva, Mário Costa Cruz
1Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Pará, 1720, Campus Umuarama, Uberlândia, 38400-902, MG, Brazil.
Abstract:
Toxoplasma gondii infects a variety of different cell types in a range of different hosts. Host cell invasion by T. gondii occurs by active penetration of the host cell, a process previously described as independent of host actin polymerization. Also, the parasitophorous vacuole has been shown to resist fusion with endocytic and exocytic pathways of the host cell. ADP-ribosylation factor-6 (ARF6) belongs to the ARF family of small GTP-binding proteins. ARF6 regulates membrane trafficking and actin cytoskeleton rearrangements at the plasma membrane. Here, we have observed that ARF6 is recruited to the parasitophorous vacuole of tachyzoites of T. gondii RH strain and it also plays an important role in the parasite cell invasion with activation of PI3-kinase and recruitment of PIP(2) and PIP(3) to the parasitophorous vacuole of invading parasites. Moreover, it was verified that maintenance of host cell actin cytoskeleton integrity is important to parasite invasion.
Insights
Toxoplasma gondii invasion relies on host cell actin dynamics, involving ADP-ribosylation factor-6 (ARF6) recruitment to the vacuole. ARF6 activation of PI3-kinase is crucial for parasite entry and survival.
Area of Science:
- Cell Biology
- Parasitology
- Molecular Biology
Background:
- Toxoplasma gondii invades various host cells through active penetration.
- Host actin polymerization was previously thought to be uninvolved in T. gondii invasion.
- The parasitophorous vacuole resists host endocytic and exocytic fusion.
Purpose of the Study:
- To investigate the role of ADP-ribosylation factor-6 (ARF6) in T. gondii host cell invasion.
- To elucidate the molecular mechanisms underlying T. gondii invasion, focusing on host cell actin and membrane trafficking.
Main Methods:
- Observation of ARF6 recruitment to the parasitophorous vacuole in T. gondii RH strain tachyzoites.
- Analysis of PI3-kinase activation and phosphoinositide (PIP2 and PIP3) recruitment during invasion.
- Assessment of host cell actin cytoskeleton integrity's importance for parasite invasion.
Main Results:
- ARF6 is recruited to the parasitophorous vacuole during T. gondii invasion.
- ARF6 plays a significant role in parasite cell invasion by activating PI3-kinase.
- PI3-kinase activation leads to PIP2 and PIP3 recruitment to the parasitophorous vacuole.
- Maintaining host cell actin cytoskeleton integrity is essential for T. gondii invasion.
Conclusions:
- ARF6 is a key host factor recruited during T. gondii invasion.
- The ARF6-PI3-kinase pathway is critical for T. gondii entry and vacuole formation.
- Host actin cytoskeleton integrity is vital for successful T. gondii parasitism.
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