ArticleProceedings of the National Academy of Sciences of the United States of America2013
Critical roles of type III phosphatidylinositol phosphate kinase in murine embryonic visceral endoderm and adult intestine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Meta-analysis identifies gene-by-environment interactions as demonstrated in a study of 4,965 mice.PLoS genetics · 2014Pooled it
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- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- A high dose KRP203 induces cytoplasmic vacuoles associated with altered phosphoinositide segregation and endosome expansion.Biochemical and biophysical research communications · 2024Article
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- Multimodal action of KRP203 on phosphoinositide kinases in vitro and in cells.Biochemical and biophysical research communications · 2023Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- PIP kinases: A versatile family that demands further therapeutic attention.Advances in biological regulation · 2023Article
- Poly(ADP-ribose) Polymerase 1 Mediates Rab5 Inactivation after DNA Damage.International journal of molecular sciences · 2022Article
- Roles of PIKfyve in multiple cellular pathways.Current opinion in cell biology · 2022Review
- Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics.Nature communications · 2022Article
- PP2A-dependent TFEB activation is blocked by PIKfyve-induced mTORC1 activity.Molecular biology of the cell · 2022Article
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- A novel phosphoinositide kinase Fab1 regulates biosynthesis of pathogenic aflatoxin inVirulence · 2021Article
- Vacuolar-type proton ATPase is required for maintenance of apicobasal polarity of embryonic visceral endoderm.Scientific reports · 2021Article
- Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism.PLoS biology · 2020Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The metabolism of membrane phosphoinositides is critical for a variety of cellular processes. Phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P(2)] controls multiple steps of the intracellular membrane trafficking system in both yeast and mammalian cells. However, other than in neuronal tissues, little is known about the physiological functions of PtdIns(3,5)P(2) in mammals. Here, we provide genetic evidence that type III phosphatidylinositol phosphate kinase (PIPKIII), which produces PtdIns(3,5)P(2), is essential for the functions of polarized epithelial cells. PIPKIII-null mouse embryos die by embryonic day 8.5 because of a failure of the visceral endoderm to supply the epiblast with maternal nutrients. Similarly, although intestine-specific PIPKIII-deficient mice are born, they fail to thrive and eventually die of malnutrition. At the mechanistic level, we show that PIPKIII regulates the trafficking of proteins to a cell's apical membrane domain. Importantly, mice with intestine-specific deletion of PIPKIII exhibit diarrhea and bloody stool, and their gut epithelial layers show inflammation and fibrosis, making our mutants an improved model for inflammatory bowel diseases. In summary, our data demonstrate that PIPKIII is required for the structural and functional integrity of two different types of polarized epithelial cells and suggest that PtdIns(3,5)P(2) metabolism is an unexpected and critical link between membrane trafficking in intestinal epithelial cells and the pathogenesis of inflammatory bowel disease.
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