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The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans
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| Zeitschriftentitel: | Development |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | Development, 138, 2011, 10, S. 2003-2014 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The Company of Biologists
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| Schlagwörter: |
| author_facet |
Neukomm, Lukas Jakob Nicot, Anne-Sophie Kinchen, Jason Michael Almendinger, Johann Pinto, Sérgio Morgado Zeng, Sheng Doukoumetzidis, Kimon Tronchère, Hélène Payrastre, Bernard Laporte, Jocelyn Franck Hengartner, Michael Otmar Neukomm, Lukas Jakob Nicot, Anne-Sophie Kinchen, Jason Michael Almendinger, Johann Pinto, Sérgio Morgado Zeng, Sheng Doukoumetzidis, Kimon Tronchère, Hélène Payrastre, Bernard Laporte, Jocelyn Franck Hengartner, Michael Otmar |
|---|---|
| author |
Neukomm, Lukas Jakob Nicot, Anne-Sophie Kinchen, Jason Michael Almendinger, Johann Pinto, Sérgio Morgado Zeng, Sheng Doukoumetzidis, Kimon Tronchère, Hélène Payrastre, Bernard Laporte, Jocelyn Franck Hengartner, Michael Otmar |
| spellingShingle |
Neukomm, Lukas Jakob Nicot, Anne-Sophie Kinchen, Jason Michael Almendinger, Johann Pinto, Sérgio Morgado Zeng, Sheng Doukoumetzidis, Kimon Tronchère, Hélène Payrastre, Bernard Laporte, Jocelyn Franck Hengartner, Michael Otmar Development The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans Developmental Biology Molecular Biology |
| author_sort |
neukomm, lukas jakob |
| spelling |
Neukomm, Lukas Jakob Nicot, Anne-Sophie Kinchen, Jason Michael Almendinger, Johann Pinto, Sérgio Morgado Zeng, Sheng Doukoumetzidis, Kimon Tronchère, Hélène Payrastre, Bernard Laporte, Jocelyn Franck Hengartner, Michael Otmar 1477-9129 0950-1991 The Company of Biologists Developmental Biology Molecular Biology http://dx.doi.org/10.1242/dev.060012 <jats:p>Multicellular organisms use programmed cell death to eliminate unwanted or potentially harmful cells. Improper cell corpse removal can lead to autoimmune diseases. The development of interventional therapies that increase engulfment activity could represent an attractive approach to treat such diseases. Here, we describe mtm-1, the Caenorhabditis elegans homolog of human myotubularin 1, as a potential negative regulator of apoptotic cell corpse clearance. Loss of mtm-1 function leads to substantially reduced numbers of persistent cell corpses in engulfment mutants, which is a result of a restoration of engulfment function rather than of impaired or delayed programmed cell death. Epistatic analyses place mtm-1 upstream of the ternary GEF complex, which consists of ced-2, ced-5 and ced-12, and parallel to mig-2. Over-activation of engulfment results in the removal of viable cells that have been brought to the verge of death under limiting caspase activity. In addition, mtm-1 also promotes phagosome maturation in the hermaphrodite gonad, potentially through CED-1 receptor recycling. Finally, we show that the CED-12 PH domain can bind to PtdIns(3,5)P2 (one target of MTM-1 phosphatase activity), suggesting that MTM-1 might regulate CED-12 recruitment to the plasma membrane.</jats:p> The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in <i>C. elegans</i> Development |
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| title |
The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_unstemmed |
The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_full |
The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_fullStr |
The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_full_unstemmed |
The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_short |
The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_sort |
the phosphoinositide phosphatase mtm-1 regulates apoptotic cell corpse clearance through ced-5–ced-12 in <i>c. elegans</i> |
| topic |
Developmental Biology Molecular Biology |
| url |
http://dx.doi.org/10.1242/dev.060012 |
| publishDate |
2011 |
| physical |
2003-2014 |
| description |
<jats:p>Multicellular organisms use programmed cell death to eliminate unwanted or potentially harmful cells. Improper cell corpse removal can lead to autoimmune diseases. The development of interventional therapies that increase engulfment activity could represent an attractive approach to treat such diseases. Here, we describe mtm-1, the Caenorhabditis elegans homolog of human myotubularin 1, as a potential negative regulator of apoptotic cell corpse clearance. Loss of mtm-1 function leads to substantially reduced numbers of persistent cell corpses in engulfment mutants, which is a result of a restoration of engulfment function rather than of impaired or delayed programmed cell death. Epistatic analyses place mtm-1 upstream of the ternary GEF complex, which consists of ced-2, ced-5 and ced-12, and parallel to mig-2. Over-activation of engulfment results in the removal of viable cells that have been brought to the verge of death under limiting caspase activity. In addition, mtm-1 also promotes phagosome maturation in the hermaphrodite gonad, potentially through CED-1 receptor recycling. Finally, we show that the CED-12 PH domain can bind to PtdIns(3,5)P2 (one target of MTM-1 phosphatase activity), suggesting that MTM-1 might regulate CED-12 recruitment to the plasma membrane.</jats:p> |
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| author_facet | Neukomm, Lukas Jakob, Nicot, Anne-Sophie, Kinchen, Jason Michael, Almendinger, Johann, Pinto, Sérgio Morgado, Zeng, Sheng, Doukoumetzidis, Kimon, Tronchère, Hélène, Payrastre, Bernard, Laporte, Jocelyn Franck, Hengartner, Michael Otmar, Neukomm, Lukas Jakob, Nicot, Anne-Sophie, Kinchen, Jason Michael, Almendinger, Johann, Pinto, Sérgio Morgado, Zeng, Sheng, Doukoumetzidis, Kimon, Tronchère, Hélène, Payrastre, Bernard, Laporte, Jocelyn Franck, Hengartner, Michael Otmar |
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| description | <jats:p>Multicellular organisms use programmed cell death to eliminate unwanted or potentially harmful cells. Improper cell corpse removal can lead to autoimmune diseases. The development of interventional therapies that increase engulfment activity could represent an attractive approach to treat such diseases. Here, we describe mtm-1, the Caenorhabditis elegans homolog of human myotubularin 1, as a potential negative regulator of apoptotic cell corpse clearance. Loss of mtm-1 function leads to substantially reduced numbers of persistent cell corpses in engulfment mutants, which is a result of a restoration of engulfment function rather than of impaired or delayed programmed cell death. Epistatic analyses place mtm-1 upstream of the ternary GEF complex, which consists of ced-2, ced-5 and ced-12, and parallel to mig-2. Over-activation of engulfment results in the removal of viable cells that have been brought to the verge of death under limiting caspase activity. In addition, mtm-1 also promotes phagosome maturation in the hermaphrodite gonad, potentially through CED-1 receptor recycling. Finally, we show that the CED-12 PH domain can bind to PtdIns(3,5)P2 (one target of MTM-1 phosphatase activity), suggesting that MTM-1 might regulate CED-12 recruitment to the plasma membrane.</jats:p> |
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| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | Neukomm, Lukas Jakob Nicot, Anne-Sophie Kinchen, Jason Michael Almendinger, Johann Pinto, Sérgio Morgado Zeng, Sheng Doukoumetzidis, Kimon Tronchère, Hélène Payrastre, Bernard Laporte, Jocelyn Franck Hengartner, Michael Otmar 1477-9129 0950-1991 The Company of Biologists Developmental Biology Molecular Biology http://dx.doi.org/10.1242/dev.060012 <jats:p>Multicellular organisms use programmed cell death to eliminate unwanted or potentially harmful cells. Improper cell corpse removal can lead to autoimmune diseases. The development of interventional therapies that increase engulfment activity could represent an attractive approach to treat such diseases. Here, we describe mtm-1, the Caenorhabditis elegans homolog of human myotubularin 1, as a potential negative regulator of apoptotic cell corpse clearance. Loss of mtm-1 function leads to substantially reduced numbers of persistent cell corpses in engulfment mutants, which is a result of a restoration of engulfment function rather than of impaired or delayed programmed cell death. Epistatic analyses place mtm-1 upstream of the ternary GEF complex, which consists of ced-2, ced-5 and ced-12, and parallel to mig-2. Over-activation of engulfment results in the removal of viable cells that have been brought to the verge of death under limiting caspase activity. In addition, mtm-1 also promotes phagosome maturation in the hermaphrodite gonad, potentially through CED-1 receptor recycling. Finally, we show that the CED-12 PH domain can bind to PtdIns(3,5)P2 (one target of MTM-1 phosphatase activity), suggesting that MTM-1 might regulate CED-12 recruitment to the plasma membrane.</jats:p> The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in <i>C. elegans</i> Development |
| spellingShingle | Neukomm, Lukas Jakob, Nicot, Anne-Sophie, Kinchen, Jason Michael, Almendinger, Johann, Pinto, Sérgio Morgado, Zeng, Sheng, Doukoumetzidis, Kimon, Tronchère, Hélène, Payrastre, Bernard, Laporte, Jocelyn Franck, Hengartner, Michael Otmar, Development, The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans, Developmental Biology, Molecular Biology |
| title | The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_full | The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_fullStr | The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_full_unstemmed | The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_short | The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| title_sort | the phosphoinositide phosphatase mtm-1 regulates apoptotic cell corpse clearance through ced-5–ced-12 in <i>c. elegans</i> |
| title_unstemmed | The phosphoinositide phosphatase MTM-1 regulates apoptotic cell corpse clearance through CED-5–CED-12 in C. elegans |
| topic | Developmental Biology, Molecular Biology |
| url | http://dx.doi.org/10.1242/dev.060012 |