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LIFE 210 (38)

Apoptosis, caspases, Bcl2 proteins, IAPs

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Life Science
LIFE 210
Paul Laybourn

2 December Cells dying by apoptosis undergo characteristic morphological changes Cells shrink and condense, cytoskeleton collapses, nuclear envelope disassembly, chromatin condenses and fragments Cells form blebs Necrosis: cells die by acute insult, they swell and burst Programmed cell death eliminates unwanted cells Crucial during development. Half of the neurons normally die soon after they are formed. Example 1: sculpting the digits in a developing mouse paw Example 2: metamorphosis of a tadpole into a frog Quality control: eliminate cells that are abnormal, potentially dangerous (some lymphocytes), nonfunctional, damaged (DNA damage) Apoptotic cells are biochemically recognizable Endonucleases cleave DNA Phosphatidylserine flips from inner to outer leaflet of plasma membrane Signals macrophages to phagocytose the dying cell Release of mitochondria proteins from the intermembrane space. Cytochrome c Apoptosis depends on an intracellular protelytic cascade: caspases Procaspases are activated by proteolysis forming hetero-tetramers Initiator and executioner caspases. Amplification Targets: nuclear lamin, cytoskeletal proteins, cell-cell adhesions proteins Tissue specificity Not reversible Cell surface death receptors activate the extrinsic pathway of apoptosis Tumor necrosis factor (TNF) family of receptors. Homotrimers. Killer lymphocyte: best known example. Fas ligand. Death inducing signaling complex (DISC) Release of cytochrome c from mitochondria during apoptosis
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