Actin Myosin Cytoskeleton

By
Kakara Divya
Assistant Professor
School of Biotechnology
JNTUK

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 Actin, Myosin, and Cell Movement
• Actin filaments, usually in association with myosin, are responsible
for many types of cell movements.
• Myosin is the prototype of a molecular motor—a protein that
converts chemical energy in the form of ATP to mechanical energy,
thus generating force and movement.
• Best movement: Muscle contraction, the model for understanding
actin-myosin interactions and the motor activity of myosin
molecules.
• Interactions of actin and myosin are responsible not only for muscle
contraction but also for a variety of movements of non muscle cells,
including cell division (following mitosis, a contractile ring consisting of
actin filaments and myosin II divides the cell in two), so these
interactions play a central role in cell biology.
• The actin cytoskeleton is responsible for the crawling movements of
cells across a surface, which appear to be driven directly by actin
polymerization as well as actin-myosin interactions. 2
 Muscle Contraction
• Muscle cells are highly specialized for a single
task, contraction.
• There are three distinct types of muscle cells in
vertebrates:
Skeletal muscle, which is responsible for all
voluntary movements;
Cardiac muscle, which pumps blood from the
heart; and
Smooth muscle, which is responsible for
involuntary movements of organs such as the
stomach, intestine, uterus, and blood vessels.3
• In both skeletal and cardiac muscle, the contractile
elements of the cytoskeleton are present in highly
organized arrays that give rise to characteristic patterns of
cross-striations.

• Skeletal muscles are bundles of muscle fibers, which are

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• Most of the cytoplasm consists of myofibrils, which
are cylindrical bundles of two types of filaments: thick
filaments of myosin (about 15 nm in diameter) and
thin filaments of actin (about 7 nm in diameter).
• Each myofibril is organized as a chain of contractile
units called sarcomeres, which are responsible for the
striated appearance of skeletal and cardiac muscle.
• The sarcomeres (which are approximately 2.3 μm
long) consist of several distinct regions, discernible by
electron microscopy, which provided critical insights
into the mechanism of muscle contraction (Figure)

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• The ends of each sarcomere are defined by the Z disc.
• Within each sarcomere, dark bands (called A bands because
they are anisotropic when viewed with polarized light)
alternate with light bands (called I bands for isotropic).
• These bands correspond to the presence or absence of myosin
filaments.
• The I bands contain only thin (actin) filaments, whereas the A
bands contain thick (myosin) filaments. The myosin and actin
filaments overlap in peripheral regions of the A band, whereas
a middle region (called the H zone) contains only myosin.
• The actin filaments are attached at their plus ends to the Z disc,
which includes the crosslinking protein α-actinin.
• The myosin filaments are anchored at the M line in the middle
of the sarcomere. Two additional proteins (titin and nebulin)
also contribute to sarcomere structure and stability (Figure).
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• Titin is an extremely large protein (3000 kd),
and single titin molecules extend from the M
line to the Z disc.
• These long molecules of titin are thought to
act like springs that keep the myosin filaments
centered in the sarcomere and maintain the
resting tension that allows a muscle to snap
back if overextended.
• Nebulin filaments are associated with actin
and are thought to regulate the assembly of
actin filaments by acting as rulers that
determine their length. 11
 Sliding Filament Model
• The basis for understanding muscle contraction is the sliding filament
model, first proposed in 1954 both by Andrew Huxley and Ralph
Niedergerke and by Hugh Huxley and Jean Hanson (Figure).
• During muscle contraction, each sarcomere shortens, bringing the Z discs
closer together.
• There is no change in the width of the A band, but both the I bands and the
H zone almost completely disappear.
• These changes are explained by the actin and myosin filaments sliding past
one another, so that the actin filaments move into the A band and H zone.
• Muscle contraction thus results from an interaction between the actin and
myosin filaments that generates their movement relative to one another.
• The molecular basis for this interaction is the binding of myosin to actin
filaments, allowing myosin to function as a motor that drives filament
sliding. The type of myosin present in muscle (myosin II) is a very large
protein (about 500 kd) consisting of two identical heavy chains (about 200
kd each) and two pairs of light chains (about 20 kd each) (Figure)
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• Each heavy chain consists of a globular head region
and a long α-helical tail.
• The α-helical tails of two heavy chains twist around
each other in a coiled-coil structure to form a dimer,
and two light chains associate with the neck of each
head region to form the complete myosin II
molecule.
• The thick filaments of muscle consist of several
hundred myosin molecules, associated in a parallel
staggered array by interactions between their tails
(Figure).
• The globular heads of myosin bind actin, forming
cross-bridges between the thick and thin filaments.
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• It is important to note that the orientation of myosin
molecules in the thick filaments reverses at the M line of the
sarcomere.
• The polarity of actin filaments (which are attached to Z discs
at their plus ends) similarly reverses at the M line, so the
relative orientation of myosin and actin filaments is the same
on both halves of the sarcomere.
• The motor activity of myosin moves its head groups along the
actin filament in the direction of the plus end.
• This movement slides the actin filaments from both sides of
the sarcomere toward the M line, shortening the sarcomere
and resulting in muscle contraction.
• In addition to binding actin, the myosin heads bind and
hydrolyze ATP, which provides the energy to drive filament
sliding.
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• This translation of chemical energy to
movement is mediated by changes in the
shape of myosin resulting from ATP binding.
• The generally accepted model (the swinging-
cross-bridge model) is that ATP hydrolysis
drives repeated cycles of interaction between
myosin heads and actin.
• During each cycle, conformational changes in
myosin result in the movement of myosin
heads along actin filaments.

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The cycle starts with myosin (in the absence
of ATP) tightly bound to actin.

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• ATP binding dissociates the myosin-actin complex and
the hydrolysis of ATP then induces a conformational
change in myosin.
• This change affects the neck region of myosin that binds
the light chains (Figure), which acts as a lever arm to
displace the myosin head by about 5 nm.
• The products of hydrolysis (ADP and Pi) remain bound to
the myosin head, which is said to be in the “cocked”
position.
• The myosin head then rebinds at a new position on the
actin filament, resulting in the release of ADP and Pi and
triggering the “power stroke,” in which the myosin head
returns to its initial conformation, thereby sliding the
actin filament toward the M line of the sarcomere.
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• Regulation of muscle contraction in striated muscles:
The contraction of skeletal muscle is triggered by nerve
impulses, which stimulate the release of Ca2+ from the
sarcoplasmic reticulum— a specialized network of
internal membranes, similar to the endoplasmic
reticulum, that stores high concentrations of Ca2+ ions.
• The release of Ca2+ from the sarcoplasmic reticulum
increases the concentration of Ca2+ in the cytosol from
approximately 10- 7 to 10-5M.
• The increased Ca2+ concentration signals muscle
contraction via the action of two accessory proteins
bound to the actin filaments: tropomyosin and troponin
(Figure)

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• Tropomyosin is a fibrous protein that binds lengthwise along
the groove of actin filaments.
• In striated muscle, each tropomyosin molecule is bound to
troponin, which is a complex of three polypeptides: troponin
C (Ca2+-binding), troponin I (inhibitory), and troponin T
(tropomyosin-binding).
• When the concentration of Ca2+ is low, the complex of the
troponins with tropomyosin blocks the interaction of actin
and myosin, so the muscle does not contract.
• At high concentrations, Ca2+ binding to troponin C shifts the
position of the complex, relieving this inhibition and allowing
contraction to proceed.

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• ATP binding dissociates the myosin-actin complex and the hydrolysis of ATP then
induces a conformational change in myosin.
• This change affects the neck region of myosin that binds the light chains (Figure),
which acts as a lever arm to displace the myosin head by about 5 nm.
• The products of hydrolysis (ADP and Pi) remain bound to the myosin head, which
is said to be in the “cocked” position.
• The myosin head then rebinds at a new position on the actin filament, resulting
in the release of ADP and Pi and triggering the “power stroke,” in which the
myosin head returns to its initial conformation, thereby sliding the actin filament
toward the M line of the sarcomere.
• Regulation of muscle contraction in striated muscles The contraction of skeletal
muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from
the sarcoplasmic reticulum— a specialized network of internal membranes,
similar to the endoplasmic reticulum, that stores high concentrations of Ca2+
ions.
• The release of Ca2+ from the sarcoplasmic reticulum increases the concentration
of Ca2+ in the cytosol from approximately 10- 7 to 10-5M.
• The increased Ca2+ concentration signals muscle contraction via the action of
two accessory proteins bound to the actin filaments: tropomyosin and troponin
(Figure)
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https://youtu.be/BVcgO4p88AA

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 nk yo u
Th a

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