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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

Muscular System

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Page 1: Muscular System

Muscular SystemIndependent 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.

Page 2: Muscular System

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

Page 3: Muscular System

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 fascicleFrom Wikipedia, the free encyclopediaJump to: navigation, search

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.

Page 4: Muscular System

[hide] v • d • e

Histology: muscle tissue

Striatedmuscle

Skeletalmuscle

Costamere/DAPC

Membrane/extracellular

DAP: Sarcoglycan (SGCA, SGCB, SGCD, SGCE, SGCG, SGCZ) · Dystroglycan

Sarcospan · Laminin, alpha 2

Intracellular

Dystrophin · Dystrobrevin (A, B) · Syntrophin (A, B1, B2, G1, G2) · Syncoilin · Dysbindin · Synemin/desmuslin

related: NOS1 · Caveolin 3

GeneralNeuromuscular junction · Motor unit · Muscle spindle · Excitation-contraction coupling · Sliding filament mechanism

Cardiacmuscle

Myocardium · Intercalated disc · Nebulette

General

Connective tissue

Epimysium · Fascicle · Perimysium · Endomysium

FiberMuscle fiber (intrafusal, extrafusal) · Myofibril · Microfilament/Myofilament

Sarcomere/(a, i, and h bands;z and m lines)

Myofilament (thin filament/actin, thick filament/myosin, elastic filament/titin, nebulin)

Tropomyosin

Troponin (T, C, I)

Cells Myoblast/Myocyte · Satellite cell

OtherDesmin · Sarcoplasm · Sarcolemma (T-tubule) · Sarcoplasmic reticulum

Smoothmuscle

Calmodulin · Vascular smooth muscle

Other/ungrouped

Myotilin · Telethonin · Dysferlin · Fukutin · Fukutin-related protein

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muscle, DF+DRCT navs: anat/hist/physio, acquired myopathy/congenital myopathy/neoplasia, symptoms+signs/eponymous, procRetrieved 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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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

Skeletalmuscle

Costamere/DAPC

Membrane/extracellular

DAP: Sarcoglycan (SGCA, SGCB, SGCD, SGCE, SGCG, SGCZ) · Dystroglycan

Sarcospan · Laminin, alpha 2

Intracellular

Dystrophin · Dystrobrevin (A, B) · Syntrophin (A, B1, B2, G1, G2) · Syncoilin · Dysbindin · Synemin/desmuslin

related: NOS1 · Caveolin 3

GeneralNeuromuscular junction · Motor unit · Muscle spindle · Excitation-contraction coupling · Sliding filament mechanism

Cardiacmuscle

Myocardium · Intercalated disc · Nebulette

GeneralConnective tissue

Epimysium · Fascicle · Perimysium · Endomysium

FiberMuscle fiber (intrafusal, extrafusal) · Myofibril · Microfilament/Myofilament

Sarcomere/(a, i, and h

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

Page 9: Muscular System

bands;z and m lines)

filament/titin, nebulin)

Tropomyosin

Troponin (T, C, I)

Cells Myoblast/Myocyte · Satellite cell

OtherDesmin · Sarcoplasm · Sarcolemma (T-tubule) · Sarcoplasmic reticulum

[show] v • d • e

Proteins of the cytoskeleton

Human

Microfilaments(ABPs)

Myofilament

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)

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

IFstype 1 and 2 (Cytokeratin, type I, type II) · type 3 (Desmin, GFAP, Peripherin, Vimentin) · type 4 (Internexin, Nestin, Neurofilament, Synemin, Syncoilin) · type 5 (Lamin A, B)

MicrotubulesDyneins · Kinesins · MAPs (Tau protein, Dynamin) · Tubulins · Stathmin · Tektin

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

OtherAPC · Dystrophin (Dystroglycan) · plakin (Desmoplakin, Plectin) · 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"

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Categories: Cell movement | Cell biology stubs

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ActinFrom Wikipedia, the free encyclopediaJump 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

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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

Page 14: Muscular System

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

Page 15: Muscular System

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,

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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

Page 17: Muscular System

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

Page 18: Muscular System

Biophysics 37: 65–95. doi:10.1146/annurev.biophys.37.032807.125912. PMID 18573073. http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biophys.37.032807.125912.

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, 1337. ̂ 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 26733659. ̂ 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 cytoskeletonHuman

Microfilaments(ABPs)

Myofilament

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)

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

Page 19: Muscular System

IFstype 1 and 2 (Cytokeratin, type I, type II) · type 3 (Desmin, GFAP, Peripherin, Vimentin) · type 4 (Internexin, Nestin, Neurofilament, Synemin, Syncoilin) · type 5 (Lamin A, B)

MicrotubulesDyneins · Kinesins · MAPs (Tau protein, Dynamin) · Tubulins · Stathmin · Tektin

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

OtherAPC · Dystrophin (Dystroglycan) · plakin (Desmoplakin, Plectin) · Spectrin (SPTA1, SPTAN1, SPTB, SPTBN1, SPTBN2, SPTBN4, SPTBN5) · Talin (TLN1)  · Utrophin · Vinculin

[show] v • d • e

Histology: muscle tissue

Skeletalmuscle

Costamere/DAPC

Membrane/extracellular

DAP: Sarcoglycan (SGCA, SGCB, SGCD, SGCE, SGCG, SGCZ) · Dystroglycan

Sarcospan · Laminin, alpha 2

Intracellular

Dystrophin · Dystrobrevin (A, B) · Syntrophin (A, B1, B2, G1, G2) · Syncoilin · Dysbindin · Synemin/desmuslin

related: NOS1 · Caveolin 3

GeneralNeuromuscular junction · Motor unit · Muscle spindle · Excitation-contraction coupling · Sliding filament mechanism

Cardiacmuscle

Myocardium · Intercalated disc · Nebulette

General

Connective tissue

Epimysium · Fascicle · Perimysium · Endomysium

FiberMuscle fiber (intrafusal, extrafusal) · Myofibril · Microfilament/Myofilament

Sarcomere/(a, i, and h bands;z and m lines)

Myofilament (thin filament/actin, thick filament/myosin, elastic filament/titin, nebulin)

Tropomyosin

Page 20: Muscular System

Troponin (T, C, I)

Cells Myoblast/Myocyte · Satellite cell

OtherDesmin · Sarcoplasm · Sarcolemma (T-tubule) · Sarcoplasmic reticulum

[show] v • d • e

Antigens: Autoantigens

Retrieved from "http://en.wikipedia.org/wiki/Actin"Categories: Cytoskeleton | Structural proteins | Autoantigens

Views Article Discussion Edit this page History

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Biochemistry of Metabolism: Cell Biology

Myosin

Contents of this page:Classes of myosin & basic structureMotor domain function & structureBipolar assemblies of myosin IIRegulationRoles & mechanisms of myosins I, V, & VIAmeboid 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

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repeat sequences promote dimerization by interacting to form a rod-like -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. 

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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 -sheet. Loops extending from -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.

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Consistent with the predicted conformational cycle, different conformations of the myosin head & neck have been found in crystal structures. Two examples are shown. The -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

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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.

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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

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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.

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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.

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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, T utorial &

Test Questions

Cell Biology - Course index page for students at Rensselaer

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