A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans
A cell’s size affects the likelihood that it will die. But how is cell size controlled in this context and how does cell size impact commitment to the cell death fate? We present evidence that the caspase CED-3 interacts with the RhoGEF ECT-2 in Caenorhabditis elegans neuroblasts that generate “unwa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-10-01
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| Series: | PLoS Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536578/?tool=EBI |
| _version_ | 1811226865327669248 |
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| author | Aditya Sethi Hai Wei Nikhil Mishra Ioannis Segos Eric J. Lambie Esther Zanin Barbara Conradt |
| author_facet | Aditya Sethi Hai Wei Nikhil Mishra Ioannis Segos Eric J. Lambie Esther Zanin Barbara Conradt |
| author_sort | Aditya Sethi |
| collection | DOAJ |
| description | A cell’s size affects the likelihood that it will die. But how is cell size controlled in this context and how does cell size impact commitment to the cell death fate? We present evidence that the caspase CED-3 interacts with the RhoGEF ECT-2 in Caenorhabditis elegans neuroblasts that generate “unwanted” cells. We propose that this interaction promotes polar actomyosin contractility, which leads to unequal neuroblast division and the generation of a daughter cell that is below the critical “lethal” size threshold. Furthermore, we find that hyperactivation of ECT-2 RhoGEF reduces the sizes of unwanted cells. Importantly, this suppresses the “cell death abnormal” phenotype caused by the partial loss of ced-3 caspase and therefore increases the likelihood that unwanted cells die. A putative null mutation of ced-3 caspase, however, is not suppressed, which indicates that cell size affects CED-3 caspase activation and/or activity. Therefore, we have uncovered novel sequential and reciprocal interactions between the apoptosis pathway and cell size that impact a cell’s commitment to the cell death fate. This study shows that in developing C. elegans neuroblasts, the caspase CED-3 interacts with the RhoGEF ECT-2, leading to changes in actomyosin and the unequal division of these cells. This reveals a non-canonical function of caspases, wherein they help establish ensure that the size of daughter cells fated for apoptosis is below a critical ’lethal’ threshold. |
| first_indexed | 2024-04-12T09:32:00Z |
| format | Article |
| id | doaj.art-105629fb05d44252afa96e3610800df7 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-12T09:32:00Z |
| publishDate | 2022-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-105629fb05d44252afa96e3610800df72022-12-22T03:38:20ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-10-012010A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegansAditya SethiHai WeiNikhil MishraIoannis SegosEric J. LambieEsther ZaninBarbara ConradtA cell’s size affects the likelihood that it will die. But how is cell size controlled in this context and how does cell size impact commitment to the cell death fate? We present evidence that the caspase CED-3 interacts with the RhoGEF ECT-2 in Caenorhabditis elegans neuroblasts that generate “unwanted” cells. We propose that this interaction promotes polar actomyosin contractility, which leads to unequal neuroblast division and the generation of a daughter cell that is below the critical “lethal” size threshold. Furthermore, we find that hyperactivation of ECT-2 RhoGEF reduces the sizes of unwanted cells. Importantly, this suppresses the “cell death abnormal” phenotype caused by the partial loss of ced-3 caspase and therefore increases the likelihood that unwanted cells die. A putative null mutation of ced-3 caspase, however, is not suppressed, which indicates that cell size affects CED-3 caspase activation and/or activity. Therefore, we have uncovered novel sequential and reciprocal interactions between the apoptosis pathway and cell size that impact a cell’s commitment to the cell death fate. This study shows that in developing C. elegans neuroblasts, the caspase CED-3 interacts with the RhoGEF ECT-2, leading to changes in actomyosin and the unequal division of these cells. This reveals a non-canonical function of caspases, wherein they help establish ensure that the size of daughter cells fated for apoptosis is below a critical ’lethal’ threshold.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536578/?tool=EBI |
| spellingShingle | Aditya Sethi Hai Wei Nikhil Mishra Ioannis Segos Eric J. Lambie Esther Zanin Barbara Conradt A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans PLoS Biology |
| title | A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans |
| title_full | A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans |
| title_fullStr | A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans |
| title_full_unstemmed | A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans |
| title_short | A caspase–RhoGEF axis contributes to the cell size threshold for apoptotic death in developing Caenorhabditis elegans |
| title_sort | caspase rhogef axis contributes to the cell size threshold for apoptotic death in developing caenorhabditis elegans |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536578/?tool=EBI |
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