A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut
Dietary InsP6 can modulate eukaryotic cell proliferation and has complex nutritive consequences, but its metabolism in the mammalian gastrointestinal tract is poorly understood. Therefore, we performed phylogenetic analyses of the gastrointestinal microbiome in order to search for candidate InsP6 ph...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714000382 |
| _version_ | 1818420550783991808 |
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| author | Régis Stentz Samantha Osborne Nikki Horn Arthur W.H. Li Isabelle Hautefort Roy Bongaerts Marine Rouyer Paul Bailey Stephen B. Shears Andrew M. Hemmings Charles A. Brearley Simon R. Carding |
| author_facet | Régis Stentz Samantha Osborne Nikki Horn Arthur W.H. Li Isabelle Hautefort Roy Bongaerts Marine Rouyer Paul Bailey Stephen B. Shears Andrew M. Hemmings Charles A. Brearley Simon R. Carding |
| author_sort | Régis Stentz |
| collection | DOAJ |
| description | Dietary InsP6 can modulate eukaryotic cell proliferation and has complex nutritive consequences, but its metabolism in the mammalian gastrointestinal tract is poorly understood. Therefore, we performed phylogenetic analyses of the gastrointestinal microbiome in order to search for candidate InsP6 phosphatases. We determined that prominent gut bacteria express homologs of the mammalian InsP6 phosphatase (MINPP) and characterized the enzyme from Bacteroides thetaiotaomicron (BtMinpp). We show that BtMinpp has exceptionally high catalytic activity, which we rationalize on the basis of mutagenesis studies and by determining its crystal structure at 1.9 Å resolution. We demonstrate that BtMinpp is packaged inside outer membrane vesicles (OMVs) protecting the enzyme from degradation by gastrointestinal proteases. Moreover, we uncover an example of cross-kingdom cell-to-cell signaling, showing that the BtMinpp-OMVs interact with intestinal epithelial cells to promote intracellular Ca2+ signaling. Our characterization of BtMinpp offers several directions for understanding how the microbiome serves human gastrointestinal physiology. |
| first_indexed | 2024-12-14T12:56:15Z |
| format | Article |
| id | doaj.art-6f07e18ff31c45b3ac924520daba24da |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-14T12:56:15Z |
| publishDate | 2014-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6f07e18ff31c45b3ac924520daba24da2022-12-21T23:00:33ZengElsevierCell Reports2211-12472014-02-016464665610.1016/j.celrep.2014.01.021A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian GutRégis Stentz0Samantha Osborne1Nikki Horn2Arthur W.H. Li3Isabelle Hautefort4Roy Bongaerts5Marine Rouyer6Paul Bailey7Stephen B. Shears8Andrew M. Hemmings9Charles A. Brearley10Simon R. Carding11Gut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UKGut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UKGut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UKSchool of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UKGut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UKGut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UKGut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UKDepartment of Computational and Systems Biology, John Innes Centre, Norwich NR4 7UH, UKLaboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USASchool of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UKSchool of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UKGut Health and Food Safety Programme, Institute of Food Research, Norwich NR4 7UA, UKDietary InsP6 can modulate eukaryotic cell proliferation and has complex nutritive consequences, but its metabolism in the mammalian gastrointestinal tract is poorly understood. Therefore, we performed phylogenetic analyses of the gastrointestinal microbiome in order to search for candidate InsP6 phosphatases. We determined that prominent gut bacteria express homologs of the mammalian InsP6 phosphatase (MINPP) and characterized the enzyme from Bacteroides thetaiotaomicron (BtMinpp). We show that BtMinpp has exceptionally high catalytic activity, which we rationalize on the basis of mutagenesis studies and by determining its crystal structure at 1.9 Å resolution. We demonstrate that BtMinpp is packaged inside outer membrane vesicles (OMVs) protecting the enzyme from degradation by gastrointestinal proteases. Moreover, we uncover an example of cross-kingdom cell-to-cell signaling, showing that the BtMinpp-OMVs interact with intestinal epithelial cells to promote intracellular Ca2+ signaling. Our characterization of BtMinpp offers several directions for understanding how the microbiome serves human gastrointestinal physiology.http://www.sciencedirect.com/science/article/pii/S2211124714000382 |
| spellingShingle | Régis Stentz Samantha Osborne Nikki Horn Arthur W.H. Li Isabelle Hautefort Roy Bongaerts Marine Rouyer Paul Bailey Stephen B. Shears Andrew M. Hemmings Charles A. Brearley Simon R. Carding A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut Cell Reports |
| title | A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut |
| title_full | A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut |
| title_fullStr | A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut |
| title_full_unstemmed | A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut |
| title_short | A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut |
| title_sort | bacterial homolog of a eukaryotic inositol phosphate signaling enzyme mediates cross kingdom dialog in the mammalian gut |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714000382 |
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