ArticlePLoS pathogens2014
The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple Legionella effector proteins.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
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- Membrane contact sites between chloroplasts and the pathogen interface underpin plant focal immune responses.The Plant cell · 2025Article
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- Involvement of endoplasmic reticulum and histone proteins in immunomodulation by TLR4-interacting SPA4 peptide againstInfection and immunity · 2023Article
- Organelles are miscommunicating: Membrane contact sites getting hijacked by pathogens.Virulence · 2023Review
- Legionella pneumophila-mediated host posttranslational modifications.Journal of molecular cell biology · 2023Review
- Legionella- and host-driven lipid flux at LCV-ER membrane contact sites promotes vacuole remodeling.EMBO reports · 2023Article
- Bacterial effector kinases and strategies to identify their target host substrates.Frontiers in microbiology · 2023Review
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- The TetR-type regulator AtsR is involved in multidrug response in Corynebacterium glutamicum.Microbial cell factories · 2022Article
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- Knowledge to Predict Pathogens:Microorganisms · 2022Review
- SAC1 regulates autophagosomal phosphatidylinositol-4-phosphate for xenophagy-directed bacterial clearance.Cell reports · 2021Article
- The cssR gene of Corynebacterium glutamicum plays a negative regulatory role in stress responses.Microbial cell factories · 2021Article
- Modulation of phagosome phosphoinositide dynamics by a Legionella phosphoinositide 3-kinase.EMBO reports · 2021Article
- Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa.Journal of inherited metabolic disease · 2020Article
- AThe Journal of biological chemistry · 2020Article
- Phosphoinositides and the Fate ofFrontiers in immunology · 2020Review
- ScreeningProceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The Dot/Icm system of the intracellular pathogen Legionella pneumophila has the capacity to deliver over 270 effector proteins into host cells during infection. Important questions remain as to spatial and temporal mechanisms used to regulate such a large array of virulence determinants after they have been delivered into host cells. Here we investigated several L. pneumophila effector proteins that contain a conserved phosphatidylinositol-4-phosphate (PI4P)-binding domain first described in the effector DrrA (SidM). This PI4P binding domain was essential for the localization of effectors to the early L. pneumophila-containing vacuole (LCV), and DrrA-mediated recruitment of Rab1 to the LCV required PI4P-binding activity. It was found that the host cell machinery that regulates sites of contact between the plasma membrane (PM) and the endoplasmic reticulum (ER) modulates PI4P dynamics on the LCV to control localization of these effectors. Specifically, phosphatidylinositol-4-kinase IIIα (PI4KIIIα) was important for generating a PI4P signature that enabled L. pneumophila effectors to localize to the PM-derived vacuole, and the ER-associated phosphatase Sac1 was involved in metabolizing the PI4P on the vacuole to promote the dissociation of effectors. A defect in L. pneumophila replication in macrophages deficient in PI4KIIIα was observed, highlighting that a PM-derived PI4P signature is critical for biogenesis of a vacuole that supports intracellular multiplication of L. pneumophila. These data indicate that PI4P metabolism by enzymes controlling PM-ER contact sites regulate the association of L. pneumophila effectors to coordinate early stages of vacuole biogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.