Download CYTOSKELETON

CYTOSKELETON
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SIGNIFICANCE OF CYTOSKELETON IN MEDICINE
Example:
• Cytoskeletal structure: mitotic spindle (microtubules)
* Cancer diseases therapy: taxanes & vinblastine, vincristine
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CYTOSKELETON:
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Cytoskeleton and its function
Types of cytoskeletal filaments
Structure of microtubules
Function of microtubules
Structure of intermediate filaments
Function of intermediate filaments
Structure of microfilaments
Function of microfilaments
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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.]
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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.]
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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.]
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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.]
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Mechanical properties of individual types of cytoskeletal fibers
[FIG.]
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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)
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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)
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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)
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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
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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
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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
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Drugs affecting the function of microtubules:
• Colchicine (stabilization of free tubulin)
• Vinblastine, vincristine (stabilization of free tubulin)
• Taxol (stabilization of microtubules)
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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 fibers (rope-like structure)
[FIG.]
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6. FUNCTION OF INTERMEDIATE FILAMENTS:
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Nuclear lamina: structure (lamins) and localization
function [FIG.]
Intermediate filaments in cytoplasm: tissue-specific types of proteins
function (mechanical resistance of the cell)
[FIG.]
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6. FUNCTION OF INTERMEDIATE FILAMENTS:
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Nuclear lamina: structure (lamins) and localization
function [FIG.]
Intermediate filaments in cytoplasm: tissue-specific types of proteins
function (mechanical resistance of the cell)
[FIG.]
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7. STRUCTURE OF MICROFILAMENTS:
Fibers: polymers of actin
Microfilaments: double-helix
[FIG.]
Polymerization: binding of ATP (ADP)
+ end, - end of microfilaments
Dynamic instability
[FIG.]
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7. STRUCTURE OF MICROFILAMENTS:
Fibers: polymers of actin
Microfilaments: double-helix
[FIG.]
Polymerization: binding of ATP (ADP)
+ end, - end of microfilaments
Dynamic instability
[FIG.]
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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)
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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)
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LITERATURE:
• Alberts B. et al.: Essential Cell Biology. Garland Science. New York
and London, pp. 571-607, 2010.
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