1. CYTOSKELETON 1

2. SIGNIFICANCE OF CYTOSKELETON IN MEDICINE Example: Cytoskeletal structure: mitotic spindle (microtubules) * Cancer diseases therapy: taxanes & vinblastine, vincristine 2

3. CYTOSKELETON: 1.Cytoskeleton and its function 2.Types of cytoskeletal filaments 3.Structure of microtubules 4.Function of microtubules 5.Structure of intermediate filaments 6.Function of intermediate filaments 7.Structure of microfilaments 8.Function of microfilaments 3

4. 1. CYTOSKELETON AND ITS FUNCTION: What is the cytoskeleton? Functions of cytoskeleton: Intrinsic support of the cell (“skeleton of the cell“) Movements of the cell Cell signalization Dynamic balance between monomeric units and polymeric filaments of the cytoskeleton[FIG.] 4

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6. 2. TYPES OF CYTOSKELETAL FILAMENTS: Three types of cytoskeletal filaments: Microtubules Intermediate filaments Microfilaments (actin filaments) Microtubules: Monomer: tubulin (α tubulin & β tubulin) Filament: Ø 25 nm[FIG.] Intermediate filaments: Monomers: lamins (nuclear lamina) keratins (epithelial cells and their derivates) vimentin (cells of mesenchymal origin) desmin (muscle) proteins of neurofilaments (neurons) Filament: Ø about 10 nm[FIG.] Microfilaments: Monomer: actin Filament: Ø about 7 nm[FIG.] 6

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8. 2. TYPES OF CYTOSKELETAL FILAMENTS: Three types of cytoskeletal filaments: Microtubules Intermediate filaments Microfilaments (actin filaments) Microtubules: Monomer: tubulin (α tubulin & β tubulin) Filament: Ø 25 nm[FIG.] Intermediate filaments: Monomers: lamins (nuclear lamina) keratins (epithelial cells and their derivates) vimentin (cells of mesenchymal origin) desmin (muscle) proteins of neurofilaments (neurons) Filament: Ø about 10 nm[FIG.] Microfilaments: Monomer: actin Filament: Ø about 7 nm[FIG.] 8

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10. 2. TYPES OF CYTOSKELETAL FILAMENTS: Three types of cytoskeletal filaments: Microtubules Intermediate filaments Microfilaments (actin filaments) Microtubules: Monomer: tubulin (α tubulin & β tubulin) Filament: Ø 25 nm[FIG.] Intermediate filaments: Monomers: lamins (nuclear lamina) keratins (epithelial cells and their derivates) vimentin (cells of mesenchymal origin) desmin (muscle) proteins of neurofilaments (neurons) Filament: Ø about 10 nm[FIG.] Microfilaments: Monomer: actin Filament: Ø about 7 nm[FIG.] 10

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12. Mechanical properties of individual types of cytoskeletal fibres[FIG.] 12

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14. 3. STRUCTURE OF MICROTUBULES: Protofilaments: polymer consisting of dimers of α tubulin a β tubulin Microtubule: 13 protofilaments[FIG.] Polymerization: binding of GTP (GDP) + end, - end of microtubules Dynamic instability[FIG.] MTOC (microtubules organizing center) 14

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16. 3. STRUCTURE OF MICROTUBULES: Protofilaments: polymer consisting of dimers of α tubulin a β tubulin Microtubule: 13 protofilaments[FIG.] Polymerization: binding of GTP (GDP) + end, - end of microtubules Dynamic instability[FIG.] MTOC (microtubules organizing center) 16

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18. 3. STRUCTURE OF MICROTUBULES: Protofilaments: polymer consisting of dimers of α tubulin a β tubulin Microtubule: 13 protofilaments[FIG.] Polymerization: binding of GTP (GDP) + end, - end of microtubules Dynamic instability[FIG.] MTOC (microtubules organizing center) 18

19. 4. FUNCTION OF MICROTUBULES: Mitotic spindle: centrosomes[FIG.] Flagella and cilia: structure (9 doublets +2) movement (motor protein dynein)[FIG.] Tracks for the movement of organelles: motor proteins (molecular motors) dynein a kinesin 19

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21. 4. FUNCTION OF MICROTUBULES: Mitotic spindle: centrosomes[FIG.] Flagella and cilia: structure (9 doublets +2) movement (motor protein dynein)[FIG.] Tracks for the movement of organelles: motor proteins (molecular motors) dynein a kinesin 21

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23. 4. FUNCTION OF MICROTUBULES: Mitotic spindle: centrosomes[FIG.] Flagella and cilia: structure (9 doublets +2) movement (motor protein dynein)[FIG.] Tracks for the movement of organelles: motor proteins (molecular motors) dynein a kinesin 23

24. Drugs affecting the function of microtubules: Colchicine (stabilization of free tubulin) Vinblastine, vincristine (stabilization of free tubulin) Taxol (stabilization of microtubules) 24

25. 5. STRUCTURE OF INTERMEDIATE FILAMENTS: Monomeric molecules: central α-helical domain and two peripheral globular domains Fibers: polymer of tetramers (2 antiparallel dimers) Intermediate filaments: 8 twisted fibres (rope-like structure) [FIG.] 25

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27. 6. FUNCTION OF INTERMEDIATE FILAMENTS: Nuclear lamina: structure (lamins) and localization function [FIG.] Intermediate filaments in cytoplasm: tissue-specific types of proteins function (mechanical resistance of the cell) [FIG.] 27

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29. 6. FUNCTION OF INTERMEDIATE FILAMENTS: Nuclear lamina: structure (lamins) and localization function [FIG.] Intermediate filaments in cytoplasm: tissue-specific types of proteins function (mechanical resistance of the cell) [FIG.] 29

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31. 7. STRUCTURE OF MICROFILAMENTS: Fibres: polymers of actin Microfilaments: double-helix[FIG.] Polymerization: binding of ATP (ADP) + end, - end of microfilaments Dynamic instability[FIG.] 31

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33. 7. STRUCTURE OF MICROFILAMENTS: Fibres: polymers of actin Microfilaments: double-helix[FIG.] Polymerization: binding of ATP (ADP) + end, - end of microfilaments Dynamic instability[FIG.] 33

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35. 8. FUNCTION OF MICROFILAMENTS: Microvilli Cell cortex: structure and localization function Contractile ring: cytokinesis Lamellipodia, filopodia, pseudopodia: amoeboid locomotion of the cell [FIG.] [FIG.] Contractile bundles: “muscles“ of the cell Association with motor protein myosin: motility (muscles) 35

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38. 8. FUNCTION OF MICROFILAMENTS: Microvilli Cell cortex: structure and localization function Contractile ring: cytokinesis Lamellipodia, filopodia, pseudopodia: amoeboid locomotion of the cell [FIG.] [FIG.] Contractile bundles: “muscles“ of the cell Association with motor protein myosin: motility (muscles) 38

39. LITERATURE: Alberts B. et al.: Essential Cell Biology. Garland Science. New York and London, pp. 571-607, 2010. 39