Question

How do Cells Attach to the ECM?

Integrins: Apoptosis: What are triggers? What does this cause in cell? What is importance of location of PS (phosphatidyl serine) in cell membrane? Caspases (role and examples of targets in cell) Apoptosome (look at role of cytochrome c)

Answer 1

Cells attach to the underlying ECM (extracellular matrix) through integrin-dependent junctions called focal adhesions. This attaches the actin cytoskeleton to fibers of fibronectin, and hemidesmosomes, which connect intermediate filaments to basal laminae.

Triggers of apoptosis:

1. Lack of survive signals.
2. Activation of death receptors.
3. Cell damage or stress.
4. DNA damage.

Apoptosis:

It causes:

1. cell shrinkage.
2. chromatin condensation.
3. nuclear fragmentation.
4. DNA fragmentation.
5. mRNA decay.

Phosphatidylserine is usually found on the inner leaflet surface of the plasma membrane but it is redistributed during apoptosis to the extracellular surface by a protein known as scramblase.

The interaction between Fas and FasL results in the formation of the death-inducing signaling complex (DISC), which contains the FADD, caspase-8, and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase family, and triggers the execution of apoptosis of the cell. In other types of cells (type II), the Fas-DISC starts a feedback loop that spirals into increasing release of proapoptotic factors from mitochondria and the amplified activation of caspase-8. The activation of initiator caspases requires binding to specific oligomeric activator protein. Effector caspases are activated by active initiator caspases through proteolytic cleavage. The active effector caspases then proteolytically degrade a host of intracellular proteins to carry out the cell death program.

Cytochrome c is also released from mitochondria due to formation of a channel, the mitochondrial apoptosis-induced channel (MAC), in the outer mitochondrial membrane, and serves a regulatory function as it precedes morphological change associated with apoptosis. Once cytochrome c is released it binds with Apoptotic protease activating factor – 1 (Apaf-1) and ATP, which then bind to pro-caspase-9 to create a protein complex known as an apoptosome. The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn activates the effector caspase-3.