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Filaments Of The Cytoskeleton
• Actin Filaments
• Microtubules
• Intermediate filaments
– Helical polymers of protein actin
– Hollow cylinders of protein tubulin
– Ropelike fibers of inter-mediate filament proteins
• Tubulin subunits are heterodimers of -tubulin and -tubulin• GTP bound to tubulin• Hollow cylinder of 13 parallel protofilaments• Tubulin subunits in same orientation
Microtubule Structure
• Monomeric actin subunits• ATP bound to actin subunits• Two helical protofilaments• Actin subunits in same orientation
Actin Filament Structure
Plus And Minus Ends Of Actin Filaments And Microtubules
• Polarity from regular orientation of subunits• During elongation, subunits added preferentially to plus end
Nucleotide Hydrolysis
• Free actin and tubulin subunits are triphosphate form• Association with filament stimulates nucleotide hydrolysis• Diphosphate form more likely to dissociate from end• ATP/GTP caps dependent upon rate of addition
Treadmilling
• Subunits assembled at plus end and disassembled at minus end at same rate; triphosphate cap at plus end
• Subunits travel through filament
Dynamic Instability
• Alternating states of elongation and depolymerization• Dependent on presence or hydrolysis of triphosphate cap
Drugs Affecting Actin And Microtubules
• Toxins from plants specifically affect polymerization or depolymerization
• Taxol stabilizes microtubules, used in cancer therapy
Intermediate Filament Assembly
• Dimer has central regions wound into coiled-coil
• Staggered side-by-side arrangement of two dimers forms tetramer
• Tetramer is basic subunit for assembly of filaments
Types Of Intermediate Filaments
Type Component Polypeptides Cellular Location
Epithelial type I keratins (acidic) epithelial cells and type II keratins (basic) their derivatives
Axonal neurofilament proteins neurons
Nuclear lamins A, B, and C inside surface of nuclear membrane
Vimentin-like vimentin and related variousproteins
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Keratin Genetic Diseases
Epidermolysis bullosa simplex• Defective keratin in basal layer of epidermis• Rupture of cells and blistering from mechanical stress
Polymerization Of Actin And Microtubules In Vitro
• Nucleation: slow formation of stable oligomers• Elongation: rapid addition to filament• Steady-state: same rates of polymerization and depolymerization
• Centrosome: site of nucleation
– Multiple -tubulin ring complexes
– Pair of centrioles
• Nucleate from -tubulin ring complex
Nucleation Of Microtubules
Nucleation Of Actin Filaments
• Nucleate from actin-related protein complex
Regulating Filament Elongation
• Thymosin: sequesters actin monomers• Profilin: competes with thymosin, promotes actin assembly• Other proteins bind free tubulin
• Organization into bundles or gel-like networks
• Actin-binding bundling and gel-forming proteins
Cross-Linking Actin Filaments
Myosin: Actin Based Motor Proteins
• Head domain uses ATP hydrolysis to move toward plus end• Myosin II: two heavy chains each with head domain• Myosin I: one head domain
Microtubule Based Motor Proteins
• Kinesin: moves toward plus end• Dynein: moves toward minus end;
cytoplasmic and axonemal (ciliary) types
• Cycle of ATP binding, ATP hydrolysis, and phosphate release
Mechanism Of Myosin Movement
• 9 + 2 arrangement of microtubules; outer doublets• Cross-linking proteins• Ciliary dynein
Microtubules In Cilia And Flagella
• Motor force of dynein converted to bending motion
Movement Of Cilia And Flagella
Basal Bodies
• Organizing center for microtubules in cilia and flagella• Nine triplet microtubules
• Polymerization of actin causes protrusion at front
• New contacts form with solid surface
• Back of cell contracts
Cell Migration