Phagocytosis promotes programmed cell death and is controlled by Rac signaling pathway in C. elegans

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.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2002

Author dc:creator

• Reddien, Peter W. (Peter Walthour), 1974-

Advisor dc:contributor.advisor

• H. Robert Horvitz.

• Biology.

Statement dc:rights

• 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.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/146356

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/146356