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Quran 3:7-8
Learning OBJECTIVES
At the end of today's lecture, you will be able to:
• Describe the components of cytoskeleton
• Identify the structure and functions of:
• microfilaments
• Intermediate filaments
• microtubules
ACTIN
Actin → microfilaments → globular protein
Diameter → 8 nm
Concentrated near the plasma membrane
Functions:
Muscle cells → contraction
Non muscle cells physical state of the cytosol, cell
movement, contractile rings formation in cell division.
Nucleus → chromatin and nuclear structure, regulation of
gene transcription.
polymerization
Energy-dependent process.
Actin microfilaments → filamentous or F-actin structures →
polymers of G (globular) actin.
After the G-actin monomer has polymerized onto the F-actin
polymer, ATP is hydrolyzed
structure
F-actin filament → two strands of identical G-actin monomers
The ends of F-actin filaments are nonidentical.
The plus (+) end → G-actin monomers are added
Minus (−) end → subtraction of G-actin monomers
steps
Three phases: (i) lag, (ii) polymerization (iii) steady state
Lag phase → 3 G-actin monomers → nucleation site
Polymerization phase → G-actin monomers + end.
Steady state addition and subtraction at same rate
Treadmilling
The process of addition and subtraction of G-actin monomers
Fungal products
Mushrooms Amanita phalloides→ death caps →Toxin
Phalloidin
Early symptoms → gastrointestinal
4-8 day → liver, kidney failure, and death.
Phalloidin → binds to F-actin polymers → excessive
polymerization → inhibition of actin → inhibit cell movement
Phalloidin → imaging tool to identify actin
cytochalasins → used to inhibit cell movement, division and to
induce programmed cell death.
Actin-bindIng proteins
Regulate the structure of actin
Regulators of the gel/sol of the cytosol:
Cytosol as gel → more firm state
Sol → a more soluble state, less structured (more fragmented)
actin
Cofilin and gelsolin: actin → smaller sized fragments , in the
presence of calcium
Spectrin: Stability, strength and support
Dystrophin
In skeletal muscle cells, dystrophin → dystrophin-glycoprotein
complex that links actin to the basal lamina → tensile strength
to muscle fibers
Muscular dystrophy (MD): Defects in dystrophin → muscle
wasting
Examples: Duchenne MD and Becker MD
X-linked recessive traits
Contraction
Tightening & shortening to produce a pulling force
Actin and myosin cyclic interaction
Myosin head domain → interacts with actin
Tail → ATP-binding site
Functions of contraction
Stability, shape
Wound healing
Cell division (contractile ring)
Intermediate filaments
10-nm diameter
> actin microfilaments, < microtubules.
Located in the cytosol
Provide structural stability
Nuclear lamins → strength to the nucleus.
structure
formed by α-helical rod-like fibrous protein subunits
2 subunits → coiled coils dimers
Tetramer: 2 coiled-coil dimer association in an antiparallel
orientation.
Eight tetramers → mature filament.
No energy is required for the assembly
Found into stable structures.
Lack polarity
Six Types
Microtubules
Functions:
Involved in:
chromosomal movements
Formation of cilia and flagella
Movement and transport of intracellular organelles and
vesicles
Centrosome (in nucleus) → coordinate & regulate their
number, location, and cytoplasmic orientation
Structure
Resembles a hollow cylindrical tube.
Protein heterodimer → α and β tubulin
αβ tubulin assemble → protofilaments.
13 protofilaments cylindrical microtubule
A ring of 13 tubulin molecules embedded in the centrosome,
forms the nucleation site onto which the microtubule is built
GTP cap: + or leading end having tubulin with GTP
Assembly
Dynamic instability → switch back and forth between growing
and shrinking phases.
In the assembly process, tubulin heterodimers form
protofilaments.
GTP is hydrolyzed to GDP
Microtubule extend its length, until it binds organelles or
chromosomes
Disassembly
Addition of GTP-bound tubulins slows down
hydrolysis of GTP catches up and the GTP cap is lost.
New tubulin cannot bind to GDP-containing tubulin
heterodimers.
Lack of a GTP cap destabilizes the structure
Microtubule growth is stopped
Individual protofilaments peel back and curve away from the
center
Functions
Chromosomal movements: pull and push chromosomes in
dividing cells
In mitosis nuclear envelope breaks down
Cytoplasmic microtubules Reassemble as dynamic mitotic
spindles
Specified roles.
Polar microtubules keep the spindle apart
Kinetochore microtubules attach to the chromosomes
Astral microtubules position the spindle
Mitotic spindle poisons
Colchicine (given in Gout): binds to the unpolymerized tubulin
molecules → mitotic spindle broken down → no cell division
Anti-cancer drugs: vinblastine, vincristine, and Taxol bind with
tubulin
Inability of microtubules to undergo structural changes →
arrest of cell division
Learning material
Cell and Molecular Biology (Lippincott’s Illustrated Reviews)
Summary
Components of cytoskeleton
Structure and functions of:
Microfilaments
Intermediate filaments
Microtubules
ACTIN functions
Contraction
Functions of contraction
Stability, shape, heart beat
Wound healing
Cell division (contractile ring)
Non muscle cells cell movement, contractile rings
Nucleus → chromatin and nuclear structure, regulation of
gene transcription.
Thank you