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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Takasuga, Shunsuke Eguchi, Satoshi Sato, Yoshiko Katada, Toshiaki Yamazaki, Masakazu Iizuka, Ryota Mizuno, Katsunori Kimura, Hirotaka Chida, Shinsuke Wada, Yoh Ohnishi, Hirohide Kofuji, Satoshi Horie, Yasuo Odanaga, Eri Kawamura, Nobuyuki Sun-wada, Ge-hong Horie, Chihoko Kontani, Kenji Harada, Akihiro Suzuki, Akira Sasaki, Junko Sasaki, Takehiko |
| Description | Author Affiliation: Takasuga S ( Department of Medical Biology, Akita University Graduate School of Medicine, Akita 010-8543, Japan.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 5 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Endoderm Metabolism Intestines Phosphatidylinositol 3-Kinases Genetics Viscera Animals Cells, Cultured Embryo, Mammalian Embryology Ultrastructure Embryonic Stem Cells Gene Expression Profiling Inflammatory Bowel Diseases Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Confocal Microscopy, Electron Oligonucleotide Array Sequence Analysis Phosphatidylinositol Phosphates RNA Interference Reverse Transcriptase Polymerase Chain Reaction Time Factors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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