Phagocytosis promotes programmed cell death and is controlled by Rac signaling pathway in C. elegans
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2002
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Published: |
Massachusetts Institute of Technology
2022
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/1721.1/146356 |
| _version_ | 1826199612336111616 |
|---|---|
| author | Reddien, Peter W. (Peter Walthour), 1974- |
| author2 | Massachusetts Institute of Technology. Department of Biology. |
| author_facet | Massachusetts Institute of Technology. Department of Biology. Reddien, Peter W. (Peter Walthour), 1974- |
| author_sort | Reddien, Peter W. (Peter Walthour), 1974- |
| collection | MIT |
| description | Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2002 |
| first_indexed | 2024-09-23T11:23:00Z |
| format | Thesis |
| id | mit-1721.1/146356 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:23:00Z |
| publishDate | 2022 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1463562022-11-13T03:28:49Z Phagocytosis promotes programmed cell death and is controlled by Rac signaling pathway in C. elegans Reddien, Peter W. (Peter Walthour), 1974- Massachusetts Institute of Technology. Department of Biology. Massachusetts Institute of Technology. Department of Biology Biology. Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2002 Includes bibliographical references. Programmed cell death is important in development, homeostasis, and disease. In the nematode Caenorhabditis elegans, four genes, egl-1, ced-9, ced-4, and ced-3, control the execution of cell death and define a molecular pathway for cell death conserved in humans. Seven genes control the engulfment of cell deaths and define two partially redundant pathways: ced-1, ced-6, and ced-7 in one pathway and ced-2, ced-5, ced-10, and ced-12 in the other. ced-3 encodes a defining member of a family of cysteine proteases termed caspases. We performed a mutational analysis of the ced-3 caspase-encoding gene, identified residues within the CED-3 protein important for caspase function in vivo, and determined that a limited amount of cell death can occur in the complete absence of CED-3 protease activity. We discovered a role for engulfment in promoting cell death and found that in the absence of engulfment, cells could occasionally recover from the initial stages of death that are triggered by the CED-3 caspase. Our results support a new view of cell death in which engulfing cells actively promote the death process rather than simply remove dead cells. We characterized an engulfment pathway and found that ced-2 encodes an adaptor protein similar to human CrkII that physically interacts with the previously identified CED-5 DOCK180 protein and that ced-10 encodes a Rac-like GTPase. ced-10 acts downstream of ced-2 and ced-5 within engulfing cells to control the extension of cell surfaces around dying cells. (cont.) We found that ced-10 Rac is the primary Rac gene required for engulfment but acts redundantly with the mig-2 Rac-like gene and independently from ced-2 and ced-5 to control neuronal migration and axon pathfinding. We suggest Rac genes can be differentially utilized and regulated for different developmental events. We identified two new genes that promote programmed cell death from a genetic screen. The first, dpl-i, encodes a protein similar to human DP, which is the heterodimerization partner for the transcription factor E2F. The second, mcd-l, encodes a novel Zn finger-containing protein. dpl-l and mcd-l act downstream of the cell death inhibitory gene ced-9 to promote cell death. by Peter W. Reddien. Ph. D. Ph. D. Massachusetts Institute of Technology, Department of Biology 2022-11-13T03:12:53Z 2022-11-13T03:12:53Z 2002 2002 Thesis https://hdl.handle.net/1721.1/146356 50488728 MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided. http://dspace.mit.edu/handle/1721.1/7582 2 v. (375 leaves) application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biology. Reddien, Peter W. (Peter Walthour), 1974- Phagocytosis promotes programmed cell death and is controlled by Rac signaling pathway in C. elegans |
| title | Phagocytosis promotes programmed cell death and is controlled by Rac signaling pathway in C. elegans |
| title_full | Phagocytosis promotes programmed cell death and is controlled by Rac signaling pathway in C. elegans |
| title_fullStr | Phagocytosis promotes programmed cell death and is controlled by Rac signaling pathway in C. elegans |
| title_full_unstemmed | Phagocytosis promotes programmed cell death and is controlled by Rac signaling pathway in C. elegans |
| title_short | Phagocytosis promotes programmed cell death and is controlled by Rac signaling pathway in C. elegans |
| title_sort | phagocytosis promotes programmed cell death and is controlled by rac signaling pathway in c elegans |
| topic | Biology. |
| url | https://hdl.handle.net/1721.1/146356 |
| work_keys_str_mv | AT reddienpeterwpeterwalthour1974 phagocytosispromotesprogrammedcelldeathandiscontrolledbyracsignalingpathwayincelegans |