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02.15.10 Lecture 12 - The actin cytoskeleton

02.15.10 Lecture 12 - The actin cytoskeleton. Actin filaments allow cells to adopt different shapes and perform different functions. Villi. Contractile bundles. Sheet-like & Finger-like protrusions. Contractile ring. Actin filaments are thin and flexible. 7 nm in diameter

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02.15.10 Lecture 12 - The actin cytoskeleton

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  1. 02.15.10Lecture 12 - The actin cytoskeleton

  2. Actin filaments allow cells to adopt different shapes and perform different functions Villi Contractile bundles Sheet-like & Finger-like protrusions Contractile ring

  3. Actin filaments are thin and flexible • 7 nm in diameter • Less rigid than microtubules • Plus end - fast growing • Minus end - slow growing • Monomers polymerize into a helical chain

  4. Actin and microtubules polymerize using similar mechanisms • Monomeric actin binds to ATP • Upon polymerization, actin ATPase activity cleaves ATP to ADP • ATP hydrolysis acts as a molecular “clock” • Older actin filaments with ADP are unstable and disassemble

  5. Actin architecture and function is governed by actin-binding proteins

  6. Example: actin in microvilli

  7. Example: actin in the cell cortex

  8. Actin polymerization can produce “pushing” forces • Polymerization at the front of a cell pushes the leading edge forward • Phagocytosis - formation of pseudopods • Intracellular movement and cell-to-cell spreading of pathogens

  9. Actin polymerization drives protrusion of the cell membrane Filopodia Lamellipodia

  10. Model for actin polymerization at membranes

  11. Actin polymerization powers engulfment during phagocytosis

  12. Movement of Listeria monocytogenes • Pathogenic bacterium that colonizes the epithelial cells lining the gut • Found in contaminated dairy products • Infection can be lethal to newborns and immunocompromised individuals

  13. Listeria move on an actin-based “comet-tail”

  14. Myosins are actin-based motor proteins • Myosins convert ATP hydrolysis into movement along actin filaments • Many different classes of myosins (>30 in humans) • Some myosins move cargoes, other myosins slide actin (as in muscles) • Actin & ATP binding sites in N-terminal head domain

  15. Myosins “walk” along actin filaments

  16. Myosin I can carry organelles or slide actin filaments along the membrane

  17. Myosin II slides actin filaments to produce contractile forces

  18. Myosin-based contraction drives cytokinesis

  19. Skeletal muscle cells are packed with myofibrils, each of which contains repeating chains of sarcomeres

  20. Sarcomeres are contractile units of actin and myosin II

  21. In muscle cells, myosin II is a filament of many motors

  22. Muscle contraction is driven by myosin II

  23. The myosin cycle in muscle

  24. Contraction is activated by calcium release from the sarcoplasmic reticulum

  25. Calcium release channels are opened by a voltage-sensitive transmembrane protein in the T-tubule

  26. Contraction is regulated by a Ca+2-mediated change in the conformation of troponin

  27. Muscle contraction

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