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The Machinery at Endoplasmic Reticulum-Plasma Membrane Contact Sites Contributes to Spatial Regulation of Multiple Effector Proteins
The intracellular pathogen Legionella pneumophila encodes at least 270 effectors that modulate trafficking of the pathogen-occupied vacuole. The mechanisms by which effectors are controlled in host cells are of key interest. Spatial and temporal regulation of effector function has been proposed to involve effector binding to host phosphoinositides. We present results showing that L. pneumophila utilizes the host kinase PI4KIIIα to generate PI4P on the bacterial vacuole and this signature mediates the localization of DrrA and subsequent recruitment of the GTPase Rab1. Additionally, it was found that the host PI4P phosphatase Sac1 was involved in consuming PI4P on the vacuole, which reduced DrrA-mediated recruitment of Rab1 to the LCV. Our data supports the recent concept that PI4KIIIα is important for generation of the plasma-membrane pool of PI4P in host cells, and demonstrates a functional consequence for PI4P-binding by an L. pneumophila effector protein.
Vyšlo v časopise: The Machinery at Endoplasmic Reticulum-Plasma Membrane Contact Sites Contributes to Spatial Regulation of Multiple Effector Proteins. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004222
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004222Souhrn
The intracellular pathogen Legionella pneumophila encodes at least 270 effectors that modulate trafficking of the pathogen-occupied vacuole. The mechanisms by which effectors are controlled in host cells are of key interest. Spatial and temporal regulation of effector function has been proposed to involve effector binding to host phosphoinositides. We present results showing that L. pneumophila utilizes the host kinase PI4KIIIα to generate PI4P on the bacterial vacuole and this signature mediates the localization of DrrA and subsequent recruitment of the GTPase Rab1. Additionally, it was found that the host PI4P phosphatase Sac1 was involved in consuming PI4P on the vacuole, which reduced DrrA-mediated recruitment of Rab1 to the LCV. Our data supports the recent concept that PI4KIIIα is important for generation of the plasma-membrane pool of PI4P in host cells, and demonstrates a functional consequence for PI4P-binding by an L. pneumophila effector protein.
Zdroje
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