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Muscular System

Independent movement is a unique characteristic of animals. Most animal movement


depends on the use of muscles. Together, muscles and bones make up what is known as
the musculoskeletal system. This combination provides protection for the body's internal
organs and allows for many kinds of movement. Whether the movement is as simple as
opening the eyes or as complex as flying, each is the result of a series of electrical,
chemical, and physical interactions involving the brain, the central nervous system, and
the muscles themselves.

Muscle is the flesh, minus the fat, that covers the skeleton of vertebrate animals.
Muscles vary in size and shape and serve many different purposes. Large leg muscles
such as hamstrings and quadriceps control limb motion. Other muscles, like the heart and
the muscles of the inner ear, perform specialized involuntary functions. Despite the
variety in size and function, however, all muscles share similar characteristics.

At the highest level, the entire muscle is composed of many strands of tissue called
fascicles . These are the strands of muscle that can be seen in red meat or chicken. These
strands are made up of very small fibers. These fibers are composed of tens of thousands
of threadlike myofibrils, which can contract, relax, and lengthen.

The myofibrils are composed of up to ten million bands laid end-toend called
sarcomeres . Each sarcomere is made of overlapping thick and thin filaments called
myofilaments . The thick and thin myofilaments are made up of contractile proteins,
primarily actin and myosin .

Types of Muscle Tissue


Muscles are categorized as either voluntary or involuntary. The muscles that animals can
deliberately control are known as voluntary muscles . Those that cannot be controlled by
the animal, such as the heart, are called involuntary muscles . Vertebrates also possess
several different types of muscle tissue: cardiac, smooth, and striated or skeletal.

The muscle types are classified on the basis of their appearance when viewed through a
light microscope. Striated muscle appears striped (striated) with alternating light and
dark bands. Smooth muscle lacks the alternating light and dark bands.

Cardiac muscle.

Cardiac muscle makes up the wall of the heart, which is called the myocardium. In
humans the heart contracts approximately seventy times per minute and can pump nearly
5 liters (4.5 quarts) of blood each minute. The fibers of the heart muscle are branched and
arranged in a netlike pattern. The involuntary heart contraction is stimulated by an
electrical impulse within the heart itself at the sinoatrial node.
Smooth muscle.

Smooth muscle cells are organized into sheets of muscle lining the walls of the stomach,
intestines, blood vessels, and diaphragm, and parts of the urinary and reproductive
systems. The smooth muscle contractions push food through the digestive system,
regulate blood pressure by adjusting the diameter of blood vessels, regulate the flow of
air in the lungs and expel urine from the urinary bladder. These body functions are
involuntary and controlled by the autonomic nervous system .

Skeletal or striated muscle.

Skeletal muscle, which is muscle tissue attached to bones, makes up a large portion of an
animal's body weight— sometimes between 40 and 60 percent. Skeletal muscles move
parts of the skeleton in relation to each other. They contain abundant blood vessels that
transport oxygen and nutrients, nerve endings that carry electrical impulses from the
central nervous system, and nerve sensors that relay messages back to the brain. Skeletal
muscles are responsible for the conscious or voluntary movements of the trunk, arms and
legs, respiratory organs, eyes, and mouth-parts of the animal. They are used for such
actions as running, swimming, jumping, and lifting.

These distinctive muscle types can be observed throughout the evolution of vertebrates,
however the arrangement of muscles varies according to differing environmental and
survival needs. In fish, for example, most of the skeletal muscles fan out from either side
of the backbone. Muscle makes up nearly 60 percent of the fish's body and nearly all of it
is involved in moving the tail and spine.

As vertebrates evolved and adapted to life on land, the down-the-spine muscle


arrangement began to change. More muscle power was needed for moving the limbs.
Limb muscles became both bigger and longer. Some muscle fibers in a frog's hind legs
can be nearly a quarter as long as the frog's body, which is proportionately much longer
than the muscles in many fish. More muscles developed in the chest to be used for
breathing, as vertebrates began spending more time on land. In mammals, this led to the
development of the diaphragm, an involuntary muscle that helps to bring air into the
lungs.

How Muscles Contract


Nerves connect the spinal column to the muscle. The place where the nerve and muscle
meet is called the neuromuscular junction . Inside the muscle fibers, a signal from the
nervous system stimulates the flow of calcium, which causes the thick and thin fibers
(myofibrils) to slide across one another. When this occurs, the sarcomere shortens, which
generates a force. The contraction of an entire muscle fiber results when billions of
sarcomeres in the muscle shorten all at once.

The "sliding-filament theory" suggests that these thin and thick filaments become linked
together by molecular cross bridges, which act as levers to pull the filaments past each
other during the contraction of the muscle fiber. Myosin molecules have little pegs, called
cross bridges, that protrude from the thick filament. During contraction, another
molecule, called actin, appears to "climb" across these bridges.

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Muscle fascicle
From Wikipedia, the free encyclopedia
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Muscle fascicle

Structure of a skeletal muscle. (Fascicle labeled at bottom


right.)
Gray's subject #103 373

In anatomy, a fascicle is a bundle of skeletal muscle fibers surrounded by perimysium, a


type of connective tissue.

Specialized muscle fibers in the heart which transmit electrical impulses from the
Atrioventricular Node (AV Node) to the Purkinje Fibers are fascicles, also referred to as
bundle branches. These start as a single fascicle of fibers at the AV node called the
Bundle of His that then splits into three bundle branches: the right fascicular branch, left
anterior fascicular branch, and left posterior fascicular branch.

[edit] External links


• Fascicle at eMedicine Dictionary
• Histology at OU 77_04 - "Slide 77 skeletal muscle"
• Anatomy Atlases - Microscopic Anatomy, plate 05.83 - "Smooth Muscle"
• Diagram at kctcs.edu

This muscle article is a stub. You can help Wikipedia by expanding it.
[hide]
v•d•e
Histology: muscle tissue

DAP: Sarcoglycan (SGCA, SGCB, SGCD,


Membrane/ SGCE, SGCG, SGCZ) · Dystroglycan
extracellular
Sarcospan · Laminin, alpha 2
Costamere/
DAPC Dystrophin · Dystrobrevin (A, B) ·
Skeletal Syntrophin (A, B1, B2, G1, G2) · Syncoilin ·
muscle Intracellular Dysbindin · Synemin/desmuslin

related: NOS1 · Caveolin 3

Neuromuscular junction · Motor unit · Muscle spindle ·


General Excitation-contraction coupling · Sliding filament
mechanism

Cardiac
Myocardium · Intercalated disc · Nebulette
muscle
Striated
muscle
Connective
Epimysium · Fascicle · Perimysium · Endomysium
tissue

Muscle fiber (intrafusal, extrafusal) · Myofibril ·


Fiber
Microfilament/Myofilament

Myofilament (thin filament/actin, thick filament/myosin,


Sarcomere/
elastic filament/titin, nebulin)
(a, i, and h
General
bands;
Tropomyosin
z and m
lines)
Troponin (T, C, I)

Cells Myoblast/Myocyte · Satellite cell

Desmin · Sarcoplasm · Sarcolemma (T-tubule) ·


Other
Sarcoplasmic reticulum

Smooth
Calmodulin · Vascular smooth muscle
muscle

Other/
Myotilin · Telethonin · Dysferlin · Fukutin · Fukutin-related protein
ungrouped
muscle, DF+DRCT navs: anat/hist/physio, acquired myopathy/congenital
myopathy/neoplasia, symptoms+signs/eponymous, proc
Retrieved from "http://en.wikipedia.org/wiki/Muscle_fascicle"
Categories: Muscle stubs

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Sarcomeres
Composed of myofilaments (contractile protein filaments) whose highly organized
arrangement results in the striations observed in the single muscle fiber.

Striation Pattern
a) A Band - composed of thick and overlapping thin filaments.
b) I Band - composed of thin filaments.
c) Z Line - connects adjacent sarcomeres and anchors thin filaments.
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Myofilament
From Wikipedia, the free encyclopedia
Jump to: navigation, search

Myofilament

Myofilaments, the filaments of myofibrils constructed from proteins,[1] are of two types,
thick and thin.

• Thin filaments consist primarily of the protein actin.


• Thick filaments consist primarily of the protein myosin.
The protein complex composed of actin and myosin is sometimes referred to as
"actomyosin". In striated muscle, such as skeletal and cardiac muscle, the actin and
myosin filaments each have a specific and constant length in the order of a few
micrometers, far less than the length of the elongated muscle cell (a few millimeters in
the case of human skeletal muscle cells). The filaments are organized into repeated
subunits along the length of the myofibril. These subunits are called sarcomeres.

[edit] References
1. ^ myofilament at Dorland's Medical Dictionary

[edit] External links


• Diagrams and explanations at biomol.uci.edu
• MeSH Myofilaments

[show]
v•d•e
Histology: muscle tissue

DAP: Sarcoglycan (SGCA, SGCB, SGCD, SGCE,


Membrane/ SGCG, SGCZ) · Dystroglycan
extracellular
Sarcospan · Laminin, alpha 2
Costamere/
DAPC Dystrophin · Dystrobrevin (A, B) · Syntrophin (A, B1,
Skeletal
B2, G1, G2) · Syncoilin · Dysbindin ·
muscle
Intracellular Synemin/desmuslin

related: NOS1 · Caveolin 3

Neuromuscular junction · Motor unit · Muscle spindle · Excitation-


General
contraction coupling · Sliding filament mechanism

Cardiac
Myocardium · Intercalated disc · Nebulette
muscle

General Connective
Epimysium · Fascicle · Perimysium · Endomysium
tissue

Muscle fiber (intrafusal, extrafusal) · Myofibril ·


Fiber
Microfilament/Myofilament

Sarcomere/Myofilament (thin filament/actin, thick filament/myosin, elastic


(a, i, and h
filament/titin, nebulin)
bands;
z and m Tropomyosin
lines)
Troponin (T, C, I)

Cells Myoblast/Myocyte · Satellite cell

Desmin · Sarcoplasm · Sarcolemma (T-tubule) · Sarcoplasmic


Other
reticulum

[show]
v•d•e
Proteins of the cytoskeleton

Actins (A1, A2, B, C1, G1, G2)

Myosins (1A, 1B, 1C, MYH1, MYH2, MYH3, MYH4,


MYH6, MYH7, MYH7B, MYH8, MYH9, MYH10,
MYH11, MYH13, MYH14, MYH15, MYH16)
Myofilament
Microfilaments Tropomodulin (1, 2, 3, 4) · Troponin (T 1 2 3, C 1 2, I 1 2
(ABPs) 3) · Tropomyosin (1, 2, 3, 4)

other related: Actinin (1, 2, 3, 4) · Arp2/3 complex · actin


depolymerizing factors (Cofilin (1, 2) · Destrin) · Gelsolin ·
Profilin (1, 2)

Other Wiskott-Aldrich syndrome protein

type 1 and 2 (Cytokeratin, type I, type II) · type 3 (Desmin, GFAP,


IFs Peripherin, Vimentin) · type 4 (Internexin, Nestin, Neurofilament,
Synemin, Syncoilin) · type 5 (Lamin A, B)

Dyneins · Kinesins · MAPs (Tau protein, Dynamin) · Tubulins ·


Microtubules
Stathmin · Tektin

Alpha catenin · Beta catenin · Plakoglobin (gamma catenin) · Delta


Catenins
catenin

APC · Dystrophin (Dystroglycan) · plakin (Desmoplakin, Plectin) ·


Other Spectrin (SPTA1, SPTAN1, SPTB, SPTBN1, SPTBN2, SPTBN4,
SPTBN5) · Talin (TLN1) · Utrophin · Vinculin
This cell biology article is a stub. You can help Wikipedia by expanding it.
Retrieved from "http://en.wikipedia.org/wiki/Myofilament"
Categories: Cell movement | Cell biology stubs

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Actin
From Wikipedia, the free encyclopedia
Jump to: navigation, search

G-Actin (PDB code: 1j6z). ADP and the divalent cation are highlighted.
F-Actin; surface representation of 13 subunit repeat based on Ken Holmes' actin filament
model

Actin is a globular, roughly 42-kDa protein found in all eukaryotic cells (the only known
exception being nematode sperm) where it may be present at concentrations of over 100
μM. It is also one of the most highly-conserved proteins, differing by no more than 20%
in species as diverse as algae and humans. Actin is the monomeric subunit of two types
of filaments in cells: microfilaments, one of the three major components of the
cytoskeleton, and thin filaments, part of the contractile apparatus in muscle cells. Thus,
actin participates in many important cellular processes including muscle contraction, cell
motility, cell division and cytokinesis, vesicle and organelle movement, cell signaling,
and the establishment and maintenance of cell junctions and cell shape. Many of these
processes are mediated by extensive and intimate interactions of actin with cellular
membranes.[1] In vertebrates, three main groups of actin isoforms, alpha, beta, and gamma
have been identified. The alpha actins are found in muscle tissues and are a major
constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell
types as components of the cytoskeleton, and as mediators of internal cell motility.

Contents
[hide]

• 1 Formation of thin filament


• 2 Genetics
• 3 Functions
o 3.1 Directionality
o 3.2 Nucleation and Polymerization
o 3.3 Microfilaments
o 3.4 Actomyosin filaments
o 3.5 Nuclear actin
• 4 History
• 5 See also

• 6 References

[edit] Formation of thin filament


Formation of thin filament

[edit] Genetics
Principal interactions of structural proteins are at cadherin-based adherens junction. Actin
filaments are linked to α-actinin and to the membrane through vinculin. The head domain
of vinculin associates to E-cadherin via α-, β-, and γ-catenins. The tail domain of vinculin
binds to membrane lipids and to actin filaments.

The protein actin is one of the most highly conserved throughout evolution because it
interacts with a large number of other proteins, with 80.2% sequence conservation at the
gene level between Homo sapiens and Saccharomyces cerevisiae (a species of yeast), and
95% conservation of the primary structure of the protein product.

Although most yeasts have only a single actin gene, higher eukaryotes, in general,
express several isoforms of actin encoded by a family of related genes. Mammals have at
least six actin isoforms coded by separate genes,[2] which are divided into three classes
(alpha, beta and gamma) according to their isoelectric point. In general, alpha actins are
found in muscle (α-skeletal, α-aortic smooth, α-cardiac, and γ2-enteric smooth), whereas
beta and gamma isoforms are prominent in non-muscle cells (β- and γ1-cytoplasmic).
Although the amino acid sequences and in vitro properties of the isoforms are highly
similar, these isoforms cannot completely substitute for one another in vivo.[3]

The typical actin gene has an approximately 100-nucleotide 5' UTR, a 1200-nucleotide
translated region, and a 200-nucleotide 3' UTR. The majority of actin genes are
interrupted by introns, with up to 6 introns in any of 19 well-characterised locations. The
high conservation of the family makes actin the favoured model for studies comparing
the introns-early and introns-late models of intron evolution.

All non-spherical prokaryotes appear to possess genes such as MreB, which encode
homologues of actin; these genes are required for the cell's shape to be maintained. The
plasmid-derived gene ParM encodes an actin-like protein whose polymerised form is
dynamically unstable, and appears to partition the plasmid DNA into the daughter cells
during cell division by a mechanism analogous to that employed by microtubules in
eukaryotic mitosis.[4] Actin is found in both smooth and rough endoplasmic reticulums.

[edit] Functions
Actin has four main functions in cells :

• To form the most dynamic one of the three subclasses of the cytoskeleton, which
gives mechanical support to cells, and hardwires the cytoplasm with the
surroundings to support signal transduction.
• To allow cell motility (see Actoclampin molecular motors), including
phagocytosis of bacteria by macrophages.
• In muscle cells to be the scaffold on which myosin proteins generate force to
support muscle contraction.
• In non-muscle cells as a track for cargo transport myosins [non-conventional
myosins] such as myosin V and VI. Non-conventional myosins transport cargo,
such as vesicles and organelles, in a directed fashion, using ATP hydrolysis, at a
rate much faster than diffusion. Myosin V walks towards the barbed end of actin
filaments, while myosin VI walks toward the pointed end. Most actin filaments
are arranged with the barbed end toward the cellular membrane and the pointed
end toward the cellular interior. This arrangement allows myosin V to be an
effective motor for export of cargos, and myosin VI to be an effective motor for
import.

[edit] Directionality

The polarity of an actin filament can be determined by decorating the microfilament with
myosin "S1" fragments, creating barbed (+) and pointed (-) ends on the filament. An S1
fragment is composed of the head and neck domains of myosin II. Under physiologic
conditions, G-Actin is transformed to F-actin by ATP, where role of ATP is essential.

[edit] Nucleation and Polymerization

Actin polymerization and depolymerization is necessary in chemotaxis and cytokinesis.


Nucleating factors are necessary to stimulate actin polymerization. One such nucleating
factor is the ARP complex which acts as a barbed end of actin in its shape to stimulate the
nucleation of G-actin (or monomeric actin). The Arp2/3 complex can also bind to actin
filaments at 70 degrees to form new actin branches off of existing actin filaments. Also,
actin filaments themselves bind ATP, and hydrolysis of this ATP stimulates
destabilization of the polymer.

The growth of actin filaments can be regulated by thymosin and profilin. Thymosin binds
to G-actin to prevent it from polymerizing while profilin binds to G-actin to promote
monomeric addition to the barbed, plus end.

[edit] Microfilaments

Individual subunits of actin are known as globular actin (G-actin). G-actin subunits
assemble into long filamentous polymers called F-actin. Two parallel F-actin strands
must rotate 166 degrees in order for them to layer correctly on top of each other. This
gives the appearance of a double helix and, more importantly, gives rise to
microfilaments of the cytoskeleton. Microfilaments measure approximately 7 nm in
diameter with a loop of the helix repeating every 37 nm.

[edit] Actomyosin filaments

In muscle, actin is the major component of thin filaments, which, together with the motor
protein myosin (which forms thick filaments), are arranged into actomyosin myofibrils.
These fibrils comprise the mechanism of muscle contraction. Using the hydrolysis of
ATP for energy, myosin heads undergo a cycle during which they attach to thin
filaments, exerting a tension, and then depending on the load, perform a power stroke that
causes the thin filaments to slide past, shortening the muscle.

In contractile bundles, the actin-bundling protein alpha-actinin separates each thin


filament by ~35 nm. This increase in distance allows thick filaments to fit in between and
interact, enabling deformation or contraction. In deformation, one end of myosin is bound
to the plasma membrane while the other end "walks" toward the plus end of the actin
filament. This pulls the membrane into a different shape relative to the cell cortex. For
contraction, the myosin molecule is usually bound to two separate filaments and both
ends simultaneously "walk" toward their filament's plus end, sliding the actin filaments
closer to each other. This results in the shortening, or contraction, of the actin bundle (but
not the filament). This mechanism is responsible for muscle contraction and cytokinesis,
the division of one cell into two.

[edit] Nuclear actin

Actin is essential for transcription from RNA polymerases I, II and III. In Pol I
transcription, actin and myosin (MYO1C, which binds DNA) act as a molecular motor.
For Pol II transcription, β-actin is needed for the formation of the pre-initiation complex.
Pol III contains β-actin as a subunit. Actin can also be a component of chromatin
remodeling complexes as well as pre-mRNP particles (that is, precursor messenger RNA
bundled in proteins), and is involved in nuclear export of RNAs and proteins.[5]

[edit] History
Actin was first observed experimentally in 1887 by W.D. Halliburton, who extracted a
protein from muscle that 'coagulated' preparations of myosin, and that he dubbed
"myosin-ferment."[6] However, Halliburton was unable to further characterise his
findings, and the discovery of actin is credited instead to Brúnó F. Straub, a young
biochemist working in Albert Szent-Györgyi's laboratory at the Institute of Medical
Chemistry at the University of Szeged, Hungary.

In 1942, Straub developed a novel technique for extracting muscle protein that allowed
him to isolate substantial amounts of relatively-pure actin. Straub's method is essentially
the same as that used in laboratories today. Szent-Gyorgyi had previously described the
more viscous form of myosin produced by slow muscle extractions as 'activated' myosin,
and, since Straub's protein produced the activating effect, it was dubbed actin. The
hostilities of World War II meant that Szent-Gyorgyi and Straub were unable to publish
the work in Western scientific journals; it became well-known in the West only in 1945,
when it was published as a supplement to the Acta Physiologica Scandinavica.[7]

Straub continued to work on actin and in 1950 reported that actin contains bound ATP [8]
and that, during polymerisation of the protein into microfilaments, the nucleotide is
hydrolysed to ADP and inorganic phosphate (which remain bound in the microfilament).
Straub suggested that the transformation of ATP-bound actin to ADP-bound actin played
a role in muscular contraction. In fact, this is true only in smooth muscle, and was not
supported through experimentation until 2001.[9]

The crystal structure of G-actin was solved in 1990 by Kabsch and colleagues.[10] In the
same year a model for F-actin was proposed by Holmes and colleagues.[11] The model
was derived by fitting a helix of G-actin structures according to low-resolution fiber
diffraction data from the filament. Several models of the filament have been proposed
since. However there is still no high-resolution X-ray structure of F-actin.

The Listeria bacteria use the cellular machinery to move around inside the host cell, by
inducing directed polymerisation of actin by the ActA transmembrane protein, thus
pushing the bacterial cell around.

[edit] See also


• MreB - one of the actin homologues in bacteria
• Motor protein
• ACTA1 - alpha actin 1
• ACTB - beta actin
• ACTG1 - gamma actin 1

[edit] References
1. ^ Doherty GJ and McMahon HT (2008). "Mediation, Modulation and
Consequences of Membrane-Cytoskeleton Interactions". Annual Review of
Biophysics 37: 65–95. doi:10.1146/annurev.biophys.37.032807.125912. PMID
18573073.
http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biophys.37.032807.1
25912.
2. ^ Vandekerckhove J. and Weber K. (1978) At least six different actins are
expressed in a higher mammal: an analysis based on the amino acid sequence of
the amino-terminal tryptic peptide. J Mol Biol 126:783–802 Entrez Pubmed
745245
3. ^ Khaitlina SY (2001) Functional specificity of actin isoforms. Int Rev Cytol
202:35-98 Entrez Pubmed 11061563
4. ^ Garner EC et al. (2007) Reconstitution of DNA segregation driven by assembly
of a prokaryotic actin homolog. Science 315:1270-1274 Entrez Pubmed 17332412
5. ^ Zheng B, Han M, Bernier M, Wen JK (May 2009). "Nuclear actin and actin-
binding proteins in the regulation of transcription and gene expression". FEBS J.
276 (10): 2669–85. doi:10.1111/j.1742-4658.2009.06986.x. PMID 19459931.
6. ^ Halliburton, W.D. (1887) On muscle plasma. J. Physiol. 8, 133
7. ^ Szent-Gyorgyi, A. (1945) Studies on muscle. Acta Physiol Scandinav 9 (suppl.
25)
8. ^ Straub, F.B. and Feuer, G. (1950) Adenosinetriphosphate the functional group
of actin. Biochim. Biophys. Acta. 4, 455-470 Entrez Pubmed 2673365
9. ^ Bárány, M., Barron, J.T., Gu, L., and Bárány, K. (2001) Exchange of the actin-
bound nucleotide in intact arterial smooth muscle. J. Biol. Chem., 276, 48398-
48403 Entrez Pubmed 11602582
10. ^ Kabsch, W., Mannherz, E.G., Suck, D., Pai, E.F., and Holmes, K.C. (1990)
Atomic structure of the actin:DNase I complex. Nature, 347, 37-44 Entrez
Pubmed 2395459
11. ^ Holmes KC, Popp D, Gebhard W, Kabsch W. (1990) Atomic model of the actin
filament. Nature, 347, 21-2 Entrez Pubmed 2395461

[show]
v•d•e
Proteins of the cytoskeleton

Microfilaments Actins (A1, A2, B, C1, G1, G2)


(ABPs)
Myosins (1A, 1B, 1C, MYH1, MYH2, MYH3, MYH4,
MYH6, MYH7, MYH7B, MYH8, MYH9, MYH10,
MYH11, MYH13, MYH14, MYH15, MYH16)
Myofilament
Tropomodulin (1, 2, 3, 4) · Troponin (T 1 2 3, C 1 2, I 1 2
3) · Tropomyosin (1, 2, 3, 4)

other related: Actinin (1, 2, 3, 4) · Arp2/3 complex · actin


depolymerizing factors (Cofilin (1, 2) · Destrin) · Gelsolin ·
Profilin (1, 2)
Other Wiskott-Aldrich syndrome protein

type 1 and 2 (Cytokeratin, type I, type II) · type 3 (Desmin, GFAP,


IFs Peripherin, Vimentin) · type 4 (Internexin, Nestin, Neurofilament,
Synemin, Syncoilin) · type 5 (Lamin A, B)

Dyneins · Kinesins · MAPs (Tau protein, Dynamin) · Tubulins ·


Microtubules
Stathmin · Tektin

Alpha catenin · Beta catenin · Plakoglobin (gamma catenin) · Delta


Catenins
catenin

APC · Dystrophin (Dystroglycan) · plakin (Desmoplakin, Plectin) ·


Other Spectrin (SPTA1, SPTAN1, SPTB, SPTBN1, SPTBN2, SPTBN4,
SPTBN5) · Talin (TLN1) · Utrophin · Vinculin

[show]
v•d•e
Histology: muscle tissue

DAP: Sarcoglycan (SGCA, SGCB, SGCD, SGCE,


Membrane/ SGCG, SGCZ) · Dystroglycan
extracellular
Sarcospan · Laminin, alpha 2
Costamere/
DAPC Dystrophin · Dystrobrevin (A, B) · Syntrophin (A, B1,
Skeletal
B2, G1, G2) · Syncoilin · Dysbindin ·
muscle
Intracellular Synemin/desmuslin

related: NOS1 · Caveolin 3

Neuromuscular junction · Motor unit · Muscle spindle · Excitation-


General
contraction coupling · Sliding filament mechanism

Cardiac
Myocardium · Intercalated disc · Nebulette
muscle

General Connective
Epimysium · Fascicle · Perimysium · Endomysium
tissue

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Sarcomere/Myofilament (thin filament/actin, thick filament/myosin, elastic


(a, i, and h
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lines)
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Antigens: Autoantigens

Retrieved from "http://en.wikipedia.org/wiki/Actin"


Categories: Cytoskeleton | Structural proteins | Autoantigens

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Biochemistry of Metabolism: Cell Biology

Myosin
Contents of this page:
Classes of myosin & basic structure
Motor domain function & structure
Bipolar assemblies of myosin II
Regulation
Roles & mechanisms of myosins I, V, & VI
Ameboid movement

Note: In these notes references are given to page numbers in the Molecular Biology of
the Cell textbook by Alberts et al. (A).

Myosins are a large superfamily of motor proteins that move along actin filaments,
while hydrolyzing ATP. About 20 classes of myosin have been distinguished on the basis
of the sequence of amino acids in their ATP-hydrolyzing motor domains. The different
classes of myosin also differ in structure of their tail domains. Tail domains have various
functions in different myosin classes, including dimerization and other protein-protein
interactions. Only a few of the known classes of myosin will be discussed here.
See diagrams in A. p. 950, 951, a diagram accessible from the Myosin Home Page at
Cambridge University, and diagrams depicting the motor domain and neck region below.
Myosin II was first studied for its role in
muscle contraction, but it functions also in
non-muscle cells.

• Myosin II includes two heavy


chains.
o The globular motor
domain of each heavy chain catalyzes
ATP hydrolysis, and interacts with actin.

o Each heavy chain continues


into a tail domain in which heptad repeat
sequences promote dimerization by
interacting to form a rod-like α -helical
coiled coil.
• Two light chains, designated essential
and regulatory, wrap around the neck
region of each myosin II heavy chain. In
addition to regulatory roles, light chains
may help to stiffen the neck regions.
o The binding site for each light
chain is an IQ (isoleucine,
glutamine) sequence motif:
IQxxxRGxxxR.

o Myosin II light chains are


similar in structure to calmodulin,
but in many organisms have lost
the ability to bind Ca++. However,
the calmodulin-like light chains of
some myosins do bind Ca++.

Myosin I has only one heavy chain with a single globular motor domain. Its relatively
short tail lacks the heptad repeats that would be involved in dimerization via formation of
a coiled coil.

The Myosin VI tail domain includes a short segment of heptad repeats. Myosin VI is
found to be either monomeric or dimeric under different conditions.
Myosin V has two heavy chains like
myosin II. But myosin V has a
longer neck region that has 6
binding sites for calmodulin light
chains. Its shorter coiled coil region
is followed by a globular domain at
the end of each heavy chain tail.

Motor domains of most myosins move along actin filaments toward the plus ends of
the filaments. This movement is ATP-dependent and is accompanied by ATP
hydrolysis.

An exception is myosin VI, which moves toward the minus ends of actin filaments.

Proof that the head domain with attached neck is sufficient to drive movement has been
obtained in studies of isolated myosin heads, using fluorescence microscopy. Myosin
heads, detached from myosin tails by protease treatment and fixed to a glass surface,
promote gliding of actin filaments labeled with fluorescent rhodamine-phalloidin. This
movement is ATP-dependent. See Alberts et al. p. 951.

See also a movie and animation of actin filament movement driven by immobilized
myosin, in University of Vermont website.

Myosin II heads interact with actin filaments in a reaction cycle that may be
summarized as follows (diagram in A p. 955):

• ATP binding causes a conformational change that causes myosin to let go of


actin.
• The active site closes, and ATP is hydrolyzed, as a conformational change
(cocking of the head) results in myosin weakly binding actin, at a different place
on the filament.
• Pi release results in conformational change that leads to stronger myosin binding,
and the power stroke.
• ADP dissociation leaves the myosin head tightly bound to actin. In the absence of
ATP, this state results in muscle rigidity called rigor.

An animation may be viewed at a website of the Vale Lab at University of California,


San Francisco.
ATP binds to the myosin head adjacent to a 7-stranded β -
sheet. Loops extending from β -strands interact with the
adenine nucleotide.

The nucleotide-binding pocket of myosin is opposite a deep


cleft that bisects the actin-binding domain (diagram in A p.
953). Opening and closing of the cleft is proposed to cause
the head to pivot about the neck region, as occupancy of the
nucleotide-binding site changes and as myosin interacts with
and dissociates from actin.

Consistent with the predicted


conformational cycle, different
conformations of the myosin
head & neck have been found
in crystal structures. Two
examples are shown. The β -
sheet adjacent to the nucleotide-
binding site is colored magenta;
light chains are displayed as
backbone, in green & red.

Explore at right an example of a crystal structure of the


myosin head with associated light chains.

Myosin S1-ADP
Similarities in structure of the ADP/ATP-binding site
in myosin and the nucleotide binding site in the family of
small GTP-binding proteins such as Ras, have led to the
suggestion that myosin may be distantly related to the
GTP-binding proteins. There is little sequence
homology, but the structural similarity suggests a
common ancestor.

Explore at right the structure of the nucleotide-binding


domain of the proto-oncogene product Ras with bound
GDP. Compare to the structure of the myosin head
above.
Ras-GDP
Bipolar complexes of myosin II form by
interaction of antiparallel coiled coil tail
domains. These complexes may contain many
myosin molecules, as in the thick filaments of
skeletal muscle (diagram in A p. 950).

Antiparallel actin filaments may be caused


to move relative to one another, as motor
domains at the opposite ends of bipolar
myosin II complexes walk toward the plus
ends of adjacent actin filaments.

Muscle sarcomere structure and the role of


myosin II in muscle contraction will not be
discussed in detail here, since it is covered in
other courses at Rensselaer. (If you are not
familiar with the role of myosin II in muscle
see A p. 961-964.)

In non-muscle cells, myosin II (the type in muscle sarcomeres) is often found to be


associated with actin filament bundles. Existence of bipolar myosin assemblies has been
postulated. Contraction of actin filament bundles is postulated to involve myosin-
mediated sliding of antiparallel actin filaments, e.g., in each of the following:

• stress fibers, bundles of actin filaments that link to the plasma membrane at sites
where a cell attaches to the extracellular matrix (A p. 940).
• belts of actin filaments that encircle epithelial cells, associated with adhering
junctions (A p. 1071-1072).
• the contractile ring of cytokinesis, located just inside the plasma membrane at
the division furrow (A p. 1054).
• the cortical web of actin filaments, located just inside the plasma membrane in
many cells.

Regulation by phosphorylation:
• Myosin II of smooth muscle as well as non-muscle cells may be regulated by
phosphorylation of its regulatory light chains.
o Dephosphorylation stabilizes an inhibited bent conformation in which
the motor domains contact distal tail domains preventing formation of
bipolar complexes. Diagram in A p. 961.
o Phosphorylation catalyzed by Myosin Light Chain Kinase or Rho Kinase
activates by promoting transition to the extended conformation.
• Myosin II in Dictyostelium transitions to an inhibited bent conformation unable
to form bipolar filaments when residues of its tail domain are phosphorylated
via a Myosin Heavy chain Kinase.
• Myosin V (diagram in website of X. Li) and the microtubule motor protein
kinesin are also inhibited by regulated transition to bent conformations. In the
bent conformation of each of these motor proteins, interaction of a globular tail
domain with the motor domain inhibits its ATPase activity. Binding to a cargo
protein for which it has affinity promotes transition to an active, non-bent state.

Regulation by Ca++ varies, depending on the type of myosin, the tissue and the
organism. For example:

• Some myosins are regulated by binding of Ca++ to calmodulin-like light chains,


in the neck region.
• A complex of tropomyosin and troponin (which includes a calmodulin-like
protein) regulates actin-myosin interaction in skeletal muscle sarcomeres. (See A
p. 965)
• Caldesmon, a protein regulated by phosphorylation and by Ca++, controls actin-
myosin interaction in smooth muscle.

Myosins I, V, & VI bind to membranes or to macromolecular complexes via


globular tail domains. They have roles, e.g., in movements of organelles or plasma
membranes relative to actin filaments:

• Myosins I & V associate with Golgi membranes and with vesicles derived from
the Golgi, including synaptic vesicles. In mice, myosin V mutations lead to
defects in synaptic transmission.
• In skin melanocytes, myosin V is involved in movement of membrane-enclosed
pigment granules into dendritic cell extensions (A p. 959).
• Within microvilli of intestinal epithelial cells, myosin I may have a role in pulling
the plasma membrane along actin filaments bundles within the microvilli, as
they grow by addition of actin monomers at the tip (A p. 942).
• A member of the myosin I class of motor proteins (myosin Ic) has a special role
in hearing, relating to movement of membrane-embedded ion channels along the
surface of stereocilia, thin cell processes that contain actin filaments (A p. 1270).
• Myosin VI, which is unique among myosins in walking along actin filaments
toward the minus end, has a role in clathrin-mediated endocytosis (A p. 752) as
endocytic vesicles are transported inward, away from the plasma membrane.
Movement of myosin V along actin is
processive, meaning that myosin V remains
attached to an actin filament as it walks along
that filament. In contrast, myosin II is a non-
processive motor that detaches from actin at a
stage of each reaction cycle (see above). The
processive movement of myosin V is appropriate
for its role in transporting organelles along actin
filaments.

In the hand over hand stepping mechanism of


myosin V, one head domain dissociates from an
actin filament only when the other head domain
binds to the next subunit with the correct
orientation along the helical actin filament. Since
there are 13 actin subunits per helical turn, myosin
V has a relatively long step length of 74 nm. By
stepping the length of the actin helical repeat,
myosin V maintains a straight path along an actin
filament, rather than spiraling around it.

Myosin V step length has been measured by monitoring movement of individual


fluorescent labeled calmodulin light chains associated with the myosin V neck domain.
For diagrams, see article by Yildiz et al. and a University of Illinois website on research
of P. Selvin.

High resolution electron microscopy has detected conformations consistent with the
hand-over-hand stepping mechanism.

Animation: This animation of myosin V walking along an actin filament is based on


electron microscopic images of myosin V fragments, consisting of part of the tail domain
with two attached heads, attached to actin filaments in what is interpreted as different
stages of the reaction cycle. (By M. L. Walker, S. A. Burgess, J. R. Sellers, F. Wang, J. A. Hammer,
J. Trinick & P. J. Knight.)

Ameboid movement: At the leading edge


of a moving cell is the lamellipodium. Forward
extension of a lamellipodium is driven by actin
polymerization. Lamellipodia contain an
extensively branched network of actin
filaments, with their plus ends oriented toward
the plasma membrane.

Localization of proteins that participate in


generating forward movement, at the leading
edge or other regions of an advancing cell, has
been demonstrated, e.g., by fluorescent
labeling. See A p. 974-977.
Some examples discussed above and in the
notes on actin:

• Profilin promotes ADP/ATP exchange by G-actin, to yield the ATP-bound form


competent to polymerize, at the leading edge of an advancing cell.
• Arp2/3, a complex that includes actin related proteins 2 & 3, binds to the sides of
actin filaments and nucleates growth of new filaments within lamellipodia.
• Capping protein adds to the plus ends of actin filaments shortly after they are
nucleated by Arp2/3, keeping actin filaments at the leading edge short and highly
branched.
• Myosin I binds to the plasma membrane, and may pull the membrane forward as
it walks actin filaments toward the plus end (diagram above).
• Cofilin and gelsolin may sever actin filaments, providing new plus ends for
nucleation of actin filament growth and helping to keep actin filament branches
short within the lamellipodium.
Cofilin also promotes depolymerization of actin filaments further back from the
leading edge within a lamellipodium.

• Various cross-linking proteins stabilize


the actin network in lamellipodia. Pulse
labeling has shown that the newly formed
actin filaments are stable, as an advancing
lamellipodium moves past them, until
they disassemble further back from the
edge.
• Myosin II is located predominantly at the
rear end of a moving cell, or in regions
being retracted.
Contraction in these regions probably
involves sliding of antiparallel actin
filaments driven by bipolar myosin
assemblies.
When a focal adhesion fails to detach, a
fragment of cytoplasm is sometimes left
behind.
• Calpains (intracellular Ca++-activated
proteases) may degrade constituents of
focal adhesions at the rear of a moving
cell as it is pulled forward.

See FishScope website with movies.


See a website of the Institute of Molecular
Biology at Salzburg with movies, an animation
& a diagram.

Signaling in ameboid movement is complex and only a few aspects of this regulation
will be summarized here. For example:

Regulatory roles of members of the Rho family of GTP-binding proteins include:

• Rac-GTP activates Scar/Wave (a member of the WASP family of proteins),


which in turn activates Arp2/3 to nucleate formation of actin filament branches
at the leading edge of a moving cell.
• Rho-GTP activates Rho Kinase (ROCK) to phosphorylate myosin II regulatory
light chains, to promote interaction of myosin II with actin filaments. This is
essential for formation of stress fibers and contraction of these stress fibers at the
rear of a moving cell.
Rho-GTP also activates formins to promote formation of the linear actin
filaments found in stress fibers.

PIP2 (phosphatidylinositol-4,5-bisphosphate) hydrolysis by signal-activated


Phospholipase C may result in localized increases in profilin, cofilin, gelsolin, and Ca++
(due to IP3 release).

Ca++ indicator dyes have been used to show that cytosolic [Ca++] is highest at the rear of
an advancing cell, where it may activate Myosin Light Chain Kinase and calpains.
Cytosolic [Ca++] is relatively low at the leading edge of an advancing cell, where
movement is driven more by actin filament assembly.

A summary of roles of
some cell constituents in
ameboid movement is
presented at right.

See also diagrams by


Vicente-Manzanares et al.
in J. Cell Science.

For more details, see the Myosin Home Page, which provides links to additional sites
with information relating to myosin.

Copyright © 1998-2007 by Joyce J. Diwan. All rights reserved.


Additional
material
on
Myosin:
Readings,
Tutorial &
Test
Questions

Cell Biology - Course index page for students at Rensselaer