Extrinsic pathway

Definition

The extrinsic pathway is a crucial mechanism in the process of apoptosis, where cell death is initiated through external signals binding to death receptors on the cell membrane. This pathway typically involves the activation of specific receptors, such as Fas and TNF receptors, leading to a cascade of intracellular events that ultimately activate caspases, the enzymes responsible for executing the cell death program. It highlights the importance of external factors in regulating cellular life and death, connecting the roles of signaling molecules and receptors in cell cycle regulation.

5 Must Know Facts For Your Next Test

1. The extrinsic pathway is primarily activated by extracellular signals, which engage specific death receptors on the cell surface, initiating the apoptotic process.
2. Key ligands that trigger this pathway include Fas ligand (FasL) and tumor necrosis factor-alpha (TNF-α), binding to their respective receptors.
3. Once activated, death receptors recruit adaptor proteins like FADD (Fas-associated protein with death domain), leading to the formation of a death-inducing signaling complex (DISC).
4. The activation of caspase-8 is a critical step in the extrinsic pathway; it can subsequently activate downstream effector caspases like caspase-3.
5. This pathway is vital for various physiological processes, including immune response regulation and maintaining tissue homeostasis by eliminating unwanted or potentially harmful cells.

Review Questions

• How does the extrinsic pathway differ from the intrinsic pathway in terms of initiation and signaling mechanisms?
  • The extrinsic pathway differs from the intrinsic pathway primarily in its initiation mechanism; it relies on external signals like ligands binding to death receptors on the cell membrane. In contrast, the intrinsic pathway is triggered by internal stress signals, such as DNA damage or oxidative stress. This distinction highlights how cells can respond to both external threats and internal issues through different apoptotic pathways.
• Discuss the role of caspases in the extrinsic pathway and their significance in apoptosis.
  • Caspases play a central role in the extrinsic pathway as they are the key executors of apoptosis once activated. Specifically, caspase-8 initiates the apoptotic cascade by cleaving and activating downstream effector caspases like caspase-3. This cascade leads to systematic dismantling of cellular components and ultimately cell death. The precise regulation of caspase activity ensures that apoptosis occurs in a controlled manner, preventing inadvertent damage to surrounding tissues.
• Evaluate the implications of dysregulation in the extrinsic pathway for disease development and potential therapies.
  • Dysregulation of the extrinsic pathway can lead to various diseases, including cancer, where tumor cells may evade apoptosis by altering receptor expression or signaling pathways. This evasion allows cancer cells to survive despite receiving signals that would normally trigger cell death. Understanding these mechanisms opens up potential therapeutic avenues, such as targeting death receptor pathways or enhancing their signaling to induce apoptosis selectively in cancer cells, thus restoring normal regulatory processes and promoting tumor regression.

Related terms

apoptosis:

A programmed form of cell death that occurs in a regulated manner, allowing for the elimination of damaged or unnecessary cells without causing inflammation.

caspases:

A family of cysteine proteases that play essential roles in apoptosis by cleaving specific substrates, leading to the dismantling of cellular components during cell death.

intrinsic pathway:

A mechanism of apoptosis triggered by internal cellular stress signals, such as DNA damage, which leads to mitochondrial involvement and subsequent activation of caspases.