Apoptosis in Caenorhabditis elegans (C. elegans)

Apoptosis in Caenorhabditis elegans (C. elegans) has been extensively studied and has served as a foundational model for understanding programmed cell death (PCD) in multicellular organisms, including humans. In the C. elegans embryo, 131 of the 1090 cells undergo apoptosis as a part of normal development. The molecular players involved in this process are well characterized and have mammalian counterparts, making C. elegans an excellent model system.

Key Steps and Molecular Players in C. elegans Apoptosis

1. EGL-1: The Apoptosis Trigger

EGL-1 is a pro-apoptotic BH3-only protein. It is expressed in cells fated to die. EGL-1 binds to and inhibits CED-9, the main anti-apoptotic protein. This inhibition is the first step in initiating apoptosis.

2. CED-9: The Anti-Apoptotic Guard

CED-9 is a homolog of mammalian Bcl-2, a protein that prevents apoptosis. In healthy cells, CED-9 binds to CED-4 and inhibits its activation. When EGL-1 binds to CED-9, it causes CED-9 to release CED-4, allowing apoptosis to proceed.

3. CED-4: The Activator Complex

CED-4 is functionally analogous to Apaf-1 (Apoptotic protease activating factor-1) in mammals. Once released from CED-9, CED-4 oligomerizes (forms a complex) and recruits CED-3, activating it. This step is crucial for the activation of the proteolytic cascade.

4. CED-3: The Executioner Protease

CED-3 is a caspase-like cysteine protease, the only one in C. elegans. Upon activation by the CED-4 complex, CED-3 cleaves specific cellular substrates, leading to the systematic dismantling of the cell (e.g., DNA fragmentation, cytoskeletal collapse, membrane changes). CED-3 is equivalent to caspase-3 and -9 in mammals.

Summary of the Pathway (Step-by-Step)