320Fall10Lecture11 - 1 BIO 320 Cell Biology, Fall 2010 Dr....

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BIO 320 Cell Biology, Fall 2010 Dr. Thomas Bushart Week 11 1
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Programmed cell death Apoptosis (a type of PCD) I Apo + ptosis (falling away from), in Greek “p” is silent in “pt” I Helix + pteron = helicopter (“helicoter?”) The orderly breakdown and death of a cell I Cell surface alters to signal uptake by professional phagocytes (orderly clean up) 2
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PCD vs necrosis Necrotic cells leak contents I May induce inflammatory responses 3
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Roles for PCD/apoptosis Elimination of unwanted cells during development I Hand/paw sculpting, tadpole tails I Adjustments to the nervous system “Quality control” – damaged or abnormal cells Organ size maintenance with cell turnover 4
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Molecular changes DNA fragments I Forms distinctive ladders due to nucleosomes Plasma membrane changes I Phosphatidylserine ends up in outer leaflet “Eat me” signal Inhibits inflammatory response of phagocyte I Loss of “don’t eat me” signals Mitochondria I Loss of electrical potential I Freed cytochrome C 5
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Detection of changes 6
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Molecular mediators Caspases – sequence-specific proteases I Cleave at aspartic acids (asp), have cysteine (c) at active site (c+asp+ase) Obviously dangerous to have in the cell…. I Manufactured as inactive procaspases 2 Activated through cleavage at their own specific aspartic acids by caspases Amplifying proteolytic signaling cascade Secondary (excecutioner) caspases cleave nuclear lamins, activate DNAses, etc. Process is non-reversible past a certain threshold I Chopping up proteins vs modulating phosphate groups! 7
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Caspase activation 8
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Proteolytic cascade 9
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Initiator caspase activation Contain a caspase recruitment domain (CARD) Adaptor proteins bring together initiator procaspases for their mutual activation I Activation complexes I Activation leads to cleavage and fully active caspases Extrinsic and intrinsic pathways for formation of activation complexes 10
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Extrinsic pathway External signaling leads to death-inducing signaling complex (DISC) 11
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Extrinsic pathway control Cells may need to protect themselves from the
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320Fall10Lecture11 - 1 BIO 320 Cell Biology, Fall 2010 Dr....

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