8. Apoptosis Flashcards
When might hyperproliferation occur?
Embryonic development - eg cell death to form digits
When might cells become unnecessary and therefore require apoptosis?
Removal of mammary epithelium after lactation
What is the main difference between necrosis and apoptosis?
Necrosis: Unregulated, associated with inflammation, cell may burst
Apoptosis: Proactive, not associated with inflammation, cell shrinks
Summarise the mechanism of necrosis
Cytoplasmic proteases are released due to increased plasma membrane permeability –> autodigestion
What are the 2 phases of apoptosis?
Latent and Execution
Describe the latent phase of
apoptosis
Death pathways have been activated but there is no morphological change yet
Recall the visible steps of the execution of apoptosis in the intestine
- Loss of microvilli and cell-cell junctions
- Cell shrinks
- Asymmetry of plasma membrane lost due to “flipping” of lipids in membane (PTS appears on outer membrane)
- Chromatin and nuclear condensation
- DNA fragmentation
- Formation of blebs, which are “thrown off” cell
- Fragmentation into membrane-enclosed apoptotic bodies
PLASMA MEMBRANE STAYS INTACT
What is the fate of the apoptotic membrane?
Phagocytosis by macrophages - they emit chemotacticsignals as they die
What is reponsable for executing cell death?
Caspases
What is responsable for initiating the death programme?
Mitochondria and death receptors
What does “caspases” stand for?
Cysteine-dependent aspartate-directed proteases
How are caspases activated?
Proteases
What 2 groups can the caspases be divided into? Recall their specific motifs
Initiators (CARD and DED subcategories)
Effectors
What do CARD and DED stand for?
CARD = caspase recruitment domain DED = death effector domain
Recall which caspases are initiators and which are effectors
Initiators: 2, 9 = CARD; 8,10 = DED
Effectors = 1,2,3,6,7
Summarise the maturation of caspases
- Cleave inactive procaspase
2. Fold 2 large and 2 small chains = active heterotetramer
Recall 2 functions of effector caspases
Cleave protein complexes to inactivate
Enzyme activation
What are the 2 mechanisms of caspase cascade activation
Death by design or default
Describe the structure of death receptors
Have a cytoplasmic membrane with a DD (death domain)
What is needed to activate death receptors?
Death ligand eg. Fas or TNF-alpha
Recall the key adaptors for triggering apoptosis and the function and structure of each
FADD: activate apoptosis (DED + DD)
FLIP: inhibit pathway (DED x 2)
Recall the key adaptors for triggering apoptosis and the function and structure of each
FADD: activate apoptosis (DED + DD)
FLIP: inhibit pathway (DED x 2)
What is Fas?
Death receptor that is upregulated when apoptosis is triggered
Where does fas-fas-L binding occur?
Surface of cytotoxic t cells
Recall how Fas/Fas-L leads to apoptosis
- Binds on T cell –> trimerisaton
- 3 cytoplasmic DD domains recruit FADD
- FADD recruits PROcaspase 8 which interacts with its DED
- Procaspase is cleaved to activate
- Caspase 8 cleaves effector caspases to initiate death programme
