02.16.11Lecture 12 - The actin cytoskeletonActin filaments allow cells to adopt different shapes and perform different functionsVilli ContractilebundlesSheet-like &Finger-like protrusionsContractileringActin 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 chainActin 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 disassembleActin architecture and function is governed by actin-binding proteinsExample: actin in microvilliExample: actin in the cell cortexActin 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 pathogensDuring cell migration, actin polymerization pushes the leading edge forwardActin polymerization drives protrusion of the cell membrane LamellipodiaFilopodiaLamellipodia are composed of branched networks of short filaments11Model for actin polymerization at membranes in lamellipodiaFilopodia are composed of long, unbranched actin filamentsActin polymerization powers engulfment during phagocytosisMovement 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 individualsListeria move on an actin-based “comet-tail”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 domainMyosins “walk” along actin filamentsMyosin I can carry organelles or slide actin filaments along the membraneMyosin II slides actin filaments to produce contractile forcesMyosin-based contraction drives cytokinesisSkeletal muscle cells are packed with myofibrils, each of which contains repeatingSarcomeres are contractile units of actin and myosin IIIn muscle cells, myosin II is a filament of many motorsMuscle contraction is driven by myosin IIThe myosin cycle in muscleContraction is activated by calcium release from the sarcoplasmic reticulumCalcium release channels are opened by a voltage-sensitive transmembrane protein in the T-tubuleContraction is regulated by a Ca+2-mediated change in the conformation of troponinMuscle
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