Question

Which statement best describes the extrinsic pathway for apoptosis? a. Caspases recognize an environmental signal and expose their death domain. b. Death receptors recognize an environmental signal, which then leads to the activation of caspases. c. Initiator caspases digest the nuclear lamina and cytoskeleton. d. Executioner caspases are part of the death-inducing signaling complex (DISC). e. All of the above are true of the extrinsic pathway.

Short answer

(b) Death receptors recognize an environmental signal, which then leads to the activation of caspases.

Step-by-step solution

Understand the Extrinsic Pathway for Apoptosis

Go through your notes and textbooks to understand what the extrinsic pathway for apoptosis is. This is a process where external signals can trigger cell death. It starts when death ligands bind to their respective death receptors, leading to the activation of caspases, which are enzymes that lead to cell death. This process does not involve the caspases recognising an environmental signal and exposing their death domains, nor does it involve the caspases being part of the death-inducing signaling complex (DISC).

Evaluate Each Statement

Revisit each statement in the exercise and match it against what you have understood in step one. The choice that aligns with the definition and process of the extrinsic apoptotic pathway will be the correct one.

Select the Correct Statement

From your analysis, you will find that option (b) 'Death receptors recognize an environmental signal, which then leads to the activation of caspases.' is the closest to the process of the extrinsic pathway for apoptosis. Hence it is the correct answer.

Key concepts

Death Receptors

Death receptors are specialized proteins located on the surface of cells. They play a crucial role in the extrinsic apoptosis pathway, which is a process of programmed cell death triggered by external signals. These receptors are aptly named as they are involved in initiating a cell's demise.
Upon recognizing and binding with specific ligands (also called death ligands), death receptors send a powerful signal inside the cell to activate a cascade of events leading to apoptosis. This acts as a kind of "on" switch for the cell's death process.

• Death receptors belong to the tumor necrosis factor receptor (TNFR) superfamily.
• Key examples include Fas receptor (CD95) and TNF-related apoptosis-inducing ligand receptors (TRAIL receptors).

Once engaged, the death receptors start a sequence that ultimately leads to the recruitment of various signaling molecules, including a group of enzymes called caspases.

Caspases

Caspases are essential enzymes in the apoptotic process. They play a dual role of initiator and executioner within the cell's death pathway.
In the extrinsic pathway, once death receptors are activated by their specific ligands, they signal for the formation of a protein complex that involves initiator caspases, primarily caspase-8. Caspase-8 then activates downstream caspases known as executioner caspases (such as caspase-3 and caspase-7).

• Initiator caspases: These start the apoptosis signaling cascade when activated.
• Executioner caspases: These dismantle the cell by breaking down cellular components like the cytoskeleton and nuclear material.

The activation of caspases is a key feature of apoptosis that leads to the orderly disassembly of cellular components, distinguishing apoptosis from necrosis, the latter being a form of traumatic cell death.

Death-Inducing Signaling Complex (DISC)

The death-inducing signaling complex (DISC) is a pivotal structure in the extrinsic pathway to apoptosis. Once a death receptor is engaged by its ligand, DISC forms right at the cell membrane.
This complex is important because it provides the platform for recruiting and activating initiator caspases, particularly caspase-8, which are essential for pushing the apoptotic process forward.

• Formation: DISC comprises the activated death receptor, adaptor proteins (such as FADD), and procaspase-8.
• Function: DISC acts to convert procaspase-8 into its active form, caspase-8.

The assembly of the DISC is a key early step that effectively bridges the external death signal with the internal execution of apoptosis by enabling caspases to begin their work.