Programmed elimination of cells by caspase-independent cell extrusion in C. elegans
The elimination of unnecessary or defective cells from metazoans occurs during normal development and tissue homeostasis, as well as in response to infection or cellular damage. Although many cells are removed through caspase-mediated apoptosis followed by phagocytosis by engulfing cells, other mech...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/84508 https://orcid.org/0000-0002-9964-9613 |
| _version_ | 1826193623648043008 |
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| author | Hatch, Victoria Denning, Daniel Prudden Horvitz, Howard Robert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Hatch, Victoria Denning, Daniel Prudden Horvitz, Howard Robert |
| author_sort | Hatch, Victoria |
| collection | MIT |
| description | The elimination of unnecessary or defective cells from metazoans occurs during normal development and tissue homeostasis, as well as in response to infection or cellular damage. Although many cells are removed through caspase-mediated apoptosis followed by phagocytosis by engulfing cells, other mechanisms of cell elimination occur, including the extrusion of cells from epithelia through a poorly understood, possibly caspase-independent, process. Here we identify a mechanism of cell extrusion that is caspase independent and that can eliminate a subset of the Caenorhabditis elegans cells programmed to die during embryonic development. In wild-type animals, these cells die soon after their generation through caspase-mediated apoptosis. However, in mutants lacking all four C. elegans caspase genes, these cells are eliminated by being extruded from the developing embryo into the extra-embryonic space of the egg. The shed cells show apoptosis-like cytological and morphological characteristics, indicating that apoptosis can occur in the absence of caspases in C. elegans. We describe a kinase pathway required for cell extrusion involving PAR-4, STRD-1 and MOP-25.1/-25.2, the C. elegans homologues of the mammalian tumour-suppressor kinase LKB1 and its binding partners STRADα and MO25α. The AMPK-related kinase PIG-1, a possible target of the PAR-4–STRD-1–MOP-25 kinase complex, is also required for cell shedding. PIG-1 promotes shed-cell detachment by preventing the cell-surface expression of cell-adhesion molecules. Our findings reveal a mechanism for apoptotic cell elimination that is fundamentally distinct from that of canonical programmed cell death. |
| first_indexed | 2024-09-23T09:42:05Z |
| format | Article |
| id | mit-1721.1/84508 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:42:05Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/845082022-09-26T13:11:45Z Programmed elimination of cells by caspase-independent cell extrusion in C. elegans Hatch, Victoria Denning, Daniel Prudden Horvitz, Howard Robert Massachusetts Institute of Technology. Department of Biology Denning, Daniel Prudden Hatch, Victoria Horvitz, H. Robert The elimination of unnecessary or defective cells from metazoans occurs during normal development and tissue homeostasis, as well as in response to infection or cellular damage. Although many cells are removed through caspase-mediated apoptosis followed by phagocytosis by engulfing cells, other mechanisms of cell elimination occur, including the extrusion of cells from epithelia through a poorly understood, possibly caspase-independent, process. Here we identify a mechanism of cell extrusion that is caspase independent and that can eliminate a subset of the Caenorhabditis elegans cells programmed to die during embryonic development. In wild-type animals, these cells die soon after their generation through caspase-mediated apoptosis. However, in mutants lacking all four C. elegans caspase genes, these cells are eliminated by being extruded from the developing embryo into the extra-embryonic space of the egg. The shed cells show apoptosis-like cytological and morphological characteristics, indicating that apoptosis can occur in the absence of caspases in C. elegans. We describe a kinase pathway required for cell extrusion involving PAR-4, STRD-1 and MOP-25.1/-25.2, the C. elegans homologues of the mammalian tumour-suppressor kinase LKB1 and its binding partners STRADα and MO25α. The AMPK-related kinase PIG-1, a possible target of the PAR-4–STRD-1–MOP-25 kinase complex, is also required for cell shedding. PIG-1 promotes shed-cell detachment by preventing the cell-surface expression of cell-adhesion molecules. Our findings reveal a mechanism for apoptotic cell elimination that is fundamentally distinct from that of canonical programmed cell death. Damon Runyon Cancer Research Foundation (Postdoctoral Fellowship) Charles A. King Trust (Postdoctoral Fellowship) 2014-01-24T18:22:38Z 2014-01-24T18:22:38Z 2012-07 2011-04 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/84508 Denning, Daniel P., Victoria Hatch, and H. Robert Horvitz. “Programmed elimination of cells by caspase-independent cell extrusion in C. elegans.” Nature 488, no. 7410 (July 15, 2012): 226-230. https://orcid.org/0000-0002-9964-9613 en_US http://dx.doi.org/10.1038/nature11240 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Hatch, Victoria Denning, Daniel Prudden Horvitz, Howard Robert Programmed elimination of cells by caspase-independent cell extrusion in C. elegans |
| title | Programmed elimination of cells by caspase-independent cell extrusion in C. elegans |
| title_full | Programmed elimination of cells by caspase-independent cell extrusion in C. elegans |
| title_fullStr | Programmed elimination of cells by caspase-independent cell extrusion in C. elegans |
| title_full_unstemmed | Programmed elimination of cells by caspase-independent cell extrusion in C. elegans |
| title_short | Programmed elimination of cells by caspase-independent cell extrusion in C. elegans |
| title_sort | programmed elimination of cells by caspase independent cell extrusion in c elegans |
| url | http://hdl.handle.net/1721.1/84508 https://orcid.org/0000-0002-9964-9613 |
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