ArticlePloS one2013
PIKfyve regulates the endosomal localization of CpG oligodeoxynucleotides to elicit TLR9-dependent cellular responses.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 27 citations in OpenAlex.
- Targeting PIKfyve: Chemical Biology and Drug Discovery Insights.Chemical biology & drug design · 2026Review
- DNA oligonucleotides block viral entry of SARS-CoV-2 Omicron variants.PLoS pathogens · 2026Article
- Disruption of endosomal trafficking with EGA alters TLR9 cytokine response in human plasmacytoid dendritic cells.Frontiers in immunology · 2023Article
- Below the surface: The inner lives of TLR4 and TLR9.Journal of leukocyte biology · 2019Review
- Snapin promotes HIV-1 transmission from dendritic cells by dampening TLR8 signaling.The EMBO journal · 2017Article
- IRAPNature immunology · 2017Article
- TLR9 is required for MAPK/NF-κB activation but does not cooperate with TLR2 or TLR6 to induce host resistance to Brucella abortus.Journal of leukocyte biology · 2016Article
- Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity.International immunology · 2015Article
- The Fab1/PIKfyve phosphoinositide phosphate kinase is not necessary to maintain the pH of lysosomes and of the yeast vacuole.The Journal of biological chemistry · 2015Article
- CpG-oligodeoxynucleotides suppress the proliferation of A549 lung adenocarcinoma cells via toll-like receptor 9 signaling and upregulation of Runt-related transcription factor 3 expression.Biomedical reports · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TLR9 is a receptor for oligodeoxynucleotides that contain unmethylated CpG motifs (CpG). Because TLR9 resides in the endoplasmic reticulum during the quiescence state, CpG binding to TLR9 requires membrane trafficking, which includes the maturation of the CpG-containing endosome. In the present study, we examined the role of PIKfyve, a phosphatidylinositol 3-phosphate 5-kinase, in the regulation of TLR9 signaling. The PIKfyve inhibitor YM201636 inhibited co-localization of the CpG-containing endosome with LysoTracker, which stains acidic organelle, and with TLR9. YM201636 increased the co-localization of CpG with the early endosome marker EEA1 but decreased co-localization with the late endosome marker LAMP1. Similar results were obtained in Raw264.7 cells containing shRNA that targets PIKfyve. CpG-mediated phosphorylation but not lipopolysaccharide (LPS)-mediated phosphorylation of IKK, p38 MAPK, JNK and Stat3 was severely impaired by the loss of PIKfyve function. CpG-mediated expression of cytokine mRNA was also decreased in the absence of PIKfyve. These findings demonstrate a novel role of PIKfyve in TLR9 signaling.
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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.