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Cytoskeleton
Dr.rer.nat.,Dra. Asmarinah, MS.
Depart. of Medical Biology
Faculty of Medicine UI
Cytoskeleton
System of filaments in the cell, so that the cell have
to be able to
- change their shape
- move from place to place
- rearrange their internal components to grow,
divide and adapt to changing circumstances
Examples of the cytoskeleton’s function:
•Pulls the chromosoms apart at mitosis
•Splits the dividing cell into two
•Muscle contraction
Three types of cytoskeleton filaments:
1. Actin filaments = microfilaments
Determine the shape of the cell’s surface and
necessary for whole-cell locomotion
2. Microtubules
Determine the positions of membrane-enclosed
organells and direct intracellular transport
3. Intermediate filaments
Provide mechanical strength and resistance to shear
stress
Actin filaments (microfilaments)
Microtubules
Intermediate filaments
Each type of cytoskeletal filaments is constructed from
smaller protein subunits
-Microfilaments are made of subunits actin
-Mictotubules are made of subunit tubulin
-Intermediate filaments are made of smaller subunits, that
elongated and fibrous
All three types of cytoskeletal filaments are formed by
assemblying (polimerisation) of their subunits through
noncovalent linkages
Nucleation is a step in the formation of a cytoskeletal
polymer
The cytoskeleton
and changes in
cell shape
A. Filament formation from a
small protein subunits
B. Rapid reorganization of
the cytoskeleton in a cell in
response to an external
signal
The two ends of cytoskeleton filaments polymerize at
different rates
-plus end: the fast-growing end
-minus end: the slow-growing end
Within the cell, hundreds of different cytoskeletonassosiated accessory protein regulate the distribution and
dynamic behavior of the filaments, such as:
- motor protein, to move or muscle contraction
The structure of an actin monomer and microfilaments
A. The actin monomer has a nucleotide bound in a deep cleft in the
center of the molecule
B. Arrangement of monomer in a filament
C. Electron mikrographs of actin filaments
Plus end  upper cleft
Minus end  bottom cleft which bind ATP
Actin is a single globular polypeptide chain
-Found in all eukaryote cell
-Coded from many genes (polygene)
-90% amino acid homology in different spesies
-three isoform:
α  just in muscle sell
β  present in all of the cell, excl muscle cell
γ  ……………….”……………………………..
Actin-specific drug
-Phalloidin: binds and stabilizes filaments
-Cytochalasin: cap filaments plus end
-Swinholide: severs filaments
-Latrunculin: binds subunits & prevents their
polymerization
The structure of a microtubule and its subunit
A. A tubulin heterodimer is formed from α- and β-tubulin
monomer. The GTP molecule is tightly bound in α-tubulin,
but in β-tubulin is less tightly bound.
B. One tubulin subunit and one protofilaments are shown
schematically
C. The microtubule is a stiff hollow tube formed from 13
protofilaments aligned in parallel
D. A short segment of a microtubule viewed in an electron
microscope
E. Electron micrograph of a cross section of a microtubule
showing a ring of 13 distinct protofilaments
Plus end  β-tubulin
Minus end  α-tubulin
Microtubule:
-Found in eukaryote cell
-There are + 6 isoforms of α-tubulin
+ 6 isoforms of β-tubulin
coded by different gene
-Each of isoform has distinct function
-75% amino acid homology between yeast and human
Microtubule-specific drugs
-Colchicine, colcemid: binds subunits and prevents
polimerization
-Vinblastine, vincristine: binds subunits and prevents
polimerization
-Nocodazole : binds subunits and prevents polimerization
-Taxol: binds and stabilizes microtubules
A model of intermediate filament construction
A. Intermediate filaments monomer/subunit : a small
filaments that are elongated and fibrous.
B. Identical monomer form a dimer
C. 2 dimers to form an antiparallel tetramer
D. 2 tetramers packed together
E. 8 tetramer twisted in a helixal array into ropelike
filaments, which has 16 dimers in cross section
Intermediate filaments
-Assembling and disassembling mechanism not clear; might
be protein phosphorilization disassambling
Motor protein (Molecular motor)
One of cytoskeleton-associate protein
•Binds polarized filaments
•Use ATP for the cell movement
Motor protein in cytoskeleton generate cytoskeleton sliding
for
-Muscle contraction
-Cilia or flagella movement
-Cell division
Three groups of cytoskeletal motor protein:
1. Myosin: associate with microfilaments for muscle
contraction
2. Kinesin: motor protein which associate with
mictotubule, play a role in chromosom separation in
mitosis
3. Dynein: associate with microtubule, play a role in
vesicle trafficking, reposisition of organell cell like
mitochomdria as well as in cilia movement
Myosin (myosin II)
1 copi light chain  myosin head
Each of myosin head bind and hidrolisis ATP, to generate
energy for microfilament movement to plus end direction
A. Electron micrograph of a myosin II thick filaments
B. Schematic diagram of myosin molecules which are
aggregated by means of their tail regions with their head
projecting to the outside of the filaments
C. A small section of a myosin II filaments as reconstructed
from electron micrograph
Kinesin
-is similar structurally to myosin
-Most of them carry a binding site in the tail for either a
membrane-enclosed organelle or another microtubule
-Play a role in formation of spindel fiber in chromosom
separation process in mitosis
Dinein
Largest of the known molecular motor and also
fastest.Axonemal dynein can move microtubules at
remarkable rate of 14 um/sec, the fastes kinesins can move
their microtubules at about 2-3 um/sec
Flagella dan Cilia
Built from microtubules and dynein. The movement of
them is produced by bending of its core, which is called
axoneme.
The axoneme is composed by
-9 doublet microtubule
-1 pair microtubule in the central of axoneme
-Dinein, consist of 2 kind of type: outer and inner
-Another protein, such as nexin
The bending of an axoneme
Muscle contraction
Used for running, walking, swimming and flying in
vertebrates
Depend on the ATP-driven sliding of highly organized
arrays of actin filaments againts arrays of myosin
Contractile elements of the muscle cell  miofibril, is a
cylindrical structure 1 – 2 um in diameter; consist of
contractile units, called sarkomer
Skeletal muscle myofibrils
A
B
C
C
A. Electrone micrograph of longitudinal section through a
skeletal muscle
B. Detail of skeletal muscle shown sarkomer
C. Schematic diagram of a single sarkomer
Organization of accessory protein sarkomer
Titin: extends from Z disc to M Line, is closely
associated with myosin. The rest of this protein is
elastic
Nebulin: coat actin filament
Tropomodulin: cap the minus end of actin filament
Muscle Contraction
Muscle contraction depends
on the sliding of myosin
and actin filaments, and is
initiated by a sudden rise in
cytosolic Ca2+
concentration
The cycle of structural
changes used by myosin to
walk along an actin
filament
Assesory proteins in muscle cell which are activated by
increase of Ca2+ concentration :
-Tropomiosin, associated with microfilaments
-Troponin
The Mechanism of muscle contraction
Ca2+ + Troponin  conformational changes
Positional changes of tropomiosin
Miosin head binds microfilaments
Muscle contraction
Sliding-filament model of muscle contraction.
The actin (red) and myosin (green) filaments in a
sarcomer slide past one another without shortening
Thanks you