What causes the actin to be pulled toward the center of the sarcomere?
Actin filaments, usually in association with myosin, are responsible for many types of jail cell movements. Myosin is the prototype of a molecular motor—a protein that converts chemical energy in the course of ATP to mechanical free energy, thus generating force and move. The well-nigh hitting variety of such motion is muscle contraction, which has provided the model for understanding actin-myosin interactions and the motor action of myosin molecules. However, interactions of actin and myosin are responsible not only for muscle contraction merely also for a variety of movements of nonmuscle cells, including cell division, so these interactions play a central part in cell biology. Moreover, the actin cytoskeleton is responsible for the crawling movements of cells across a surface, which appear to be driven directly by actin polymerization also as actin-myosin interactions.
Muscle Wrinkle
Muscle cells are highly specialized for a single task, contraction, and it is this specialization in structure and part that has made muscle the epitome for studying movement at the cellular and molecular levels. In that location are three distinct types of muscle cells in vertebrates: skeletal musculus, which is responsible for all voluntary movements; cardiac musculus, which pumps blood from the middle; and smoothen muscle, which is responsible for involuntary movements of organs such as the tum, intestine, uterus, and claret vessels. 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. It is the label of these structures in skeletal muscle that has led to our current understanding of muscle contraction, and other actin-based cell movements, at the molecular level.
Skeletal muscles are bundles of muscle fibers, which are single large cells (approximately 50 μm in diameter and up to several centimeters in length) formed by the fusion of many individual cells during development (Figure 11.eighteen). Virtually of the cytoplasm consists of myofibrils, which are cylindrical bundles of two types of filaments: thick filaments of myosin (nigh xv nm in bore) and thin filaments of actin (almost 7 nm in diameter). Each myofibril is organized as a concatenation of contractile units chosen sarcomeres, which are responsible for the striated appearance of skeletal and cardiac muscle.
Effigy 11.eighteen
Construction of muscle cells. Muscles are composed of bundles of single big cells (called musculus fibers) that form by cell fusion and incorporate multiple nuclei. Each muscle fiber contains many myofibrils, which are bundles of actin and myosin filaments organized (more...)
The sarcomeres (which are approximately two.3 μm long) consist of several distinct regions, discernible by electron microscopy, which provided critical insights into the machinery of muscle wrinkle (Effigy 11.19). The ends of each sarcomere are defined by the Z disc. Within each sarcomere, dark bands (chosen A bands because they are anisotropic when viewed with polarized lite) alternating with light bands (chosen I bands for isotropic). These bands represent to the presence or absence of myosin filaments. The I bands contain merely thin (actin) filaments, whereas the A bands contain thick (myosin) filaments. The myosin and actin filaments overlap in peripheral regions of the A ring, whereas a middle region (called the H zone) contains merely 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.
Effigy 11.xix
Construction of the sarcomere. (A) Electron micrograph of a sarcomere. (B) Diagram showing the organization of actin (sparse) and myosin (thick) filaments in the indicated regions. (A, Frank A. Pepe/Biological Photo Service.)
Two additional proteins (titin and nebulin) as well contribute to sarcomere structure and stability (Figure 11.xx). Titin is an extremely large protein (3000 kd), and single titin molecules extend from the 1000 line to the Z disc. These long molecules of titin are thought to human action like springs that go along 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 associates of actin filaments by interim as rulers that determine their length.
Effigy 11.20
Titin and nebulin. Molecules of titin extend from the Z disc to the M line and act as springs to go along myosin filaments centered in the sarcomere. Molecules of nebulin extend from the Z disc and are thought to determine the length of associated actin filaments. (more...)
The basis for understanding musculus wrinkle is the sliding filament model, first proposed in 1954 both by Andrew Huxley and Ralph Niedergerke and past Hugh Huxley and Jean Hanson (Figure 11.21). During muscle contraction, each sarcomere shortens, bringing the Z discs closer together. There is no modify 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 1 another, then that the actin filaments motion into the A band and H zone. Muscle contraction thus results from an interaction between the actin and myosin filaments that generates their motion relative to one another. The molecular basis for this interaction is the binding of myosin to actin filaments, allowing myosin to part as a motor that drives filament sliding.
Figure 11.21
Sliding-filament model of musculus wrinkle. The actin filaments slide past the myosin filaments toward the center of the sarcomere. The upshot is shortening of the sarcomere without any modify in filament length.
The type of myosin present in muscle (myosin II) is a very big protein (about 500 kd) consisting of two identical heavy bondage (about 200 kd each) and two pairs of low-cal chains (about 20 kd each) (Figure 11.22). 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 grade the complete myosin Ii molecule.
Figure 11.22
Myosin Ii. The myosin Ii molecule consists of 2 heavy bondage and two pairs of light bondage (called the essential and regulatory light bondage). The heavy chains have globular head regions and long α-helical tails, which roll effectually each other (more...)
The thick filaments of muscle consist of several hundred myosin molecules, associated in a parallel staggered array by interactions between their tails (Figure 11.23). The globular heads of myosin demark actin, forming cross-bridges betwixt the thick and sparse filaments. Information technology is important to annotation 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 Grand line, so the relative orientation of myosin and actin filaments is the aforementioned on both halves of the sarcomere. Every bit discussed later, the motor action 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 Grand line, shortening the sarcomere and resulting in muscle contraction.
Figure 11.23
System of myosin thick filaments. Thick filaments are formed by the association of several hundred myosin II molecules in a staggered assortment. The globular heads of myosin demark actin, forming cross-bridges between the myosin and actin filaments. The (more...)
In addition to binding actin, the myosin heads bind and hydrolyze ATP, which provides the energy to bulldoze filament sliding. This translation of chemical free energy to motility 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 betwixt myosin heads and actin. During each wheel, conformational changes in myosin event in the move of myosin heads along actin filaments.
Although the molecular mechanisms are yet not fully understood, a plausible working model for myosin part has been derived both from in vitro studies of myosin movement along actin filaments (a system developed by James Spudich and Michael Sheetz) and from determination of the three-dimensional construction of myosin past Ivan Rayment and his colleagues (Figure 11.24). The cycle starts with myosin (in the absence of ATP) tightly spring to actin. ATP bounden dissociates the myosin-actin circuitous and the hydrolysis of ATP then induces a conformational modify in myosin. This alter affects the cervix region of myosin that binds the calorie-free bondage (see Figure 11.22), which acts as a lever arm to displace the myosin head by about 5 nm. The products of hydrolysis (ADP and P i ) remain bound to the myosin head, which is said to be in the "cocked" position. The myosin caput then rebinds at a new position on the actin filament, resulting in the release of ADP and P i and triggering the "ability stroke," in which the myosin caput returns to its initial conformation, thereby sliding the actin filament toward the M line of the sarcomere.
Figure 11.24
Model for myosin action. The binding of ATP dissociates myosin from actin. ATP hydrolysis then induces a conformational change that displaces the myosin head grouping. This is followed past binding of the myosin head to a new position on the actin filament (more...)
The wrinkle of skeletal muscle is triggered by nerve impulses, which stimulate the release of Caii+ from the sarcoplasmic reticulum—a specialized network of internal membranes, like to the endoplasmic reticulum, that stores high concentrations of Catwo+ ions. The release of Catwo+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-v M. The increased Ca2+ concentration signals musculus contraction via the activeness of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Effigy eleven.25). 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 circuitous of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Catwo+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, and so the musculus does not contract. At high concentrations, Ca2+ bounden to troponin C shifts the position of the complex, relieving this inhibition and allowing wrinkle to keep.
Figure xi.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated musculus, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more...)
Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-calibration versions of muscle fibers, are nowadays also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin Ii, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to i some other (Effigy 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin 2, probably by competing with filamin for bounden sites on actin.
Figure xi.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin 2 produce contraction past sliding actin filaments in opposite directions.
Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to zipper of the actin cytoskeleton to regions of prison cell-substrate and cell-cell contacts (see Figures 11.13 and 11.fourteen). The contraction of stress fibers produces tension across the jail cell, assuasive the cell to pull on a substrate (east.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is specially of import during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The about dramatic example of actin-myosin wrinkle in nonmuscle cells, however, is provided by cytokinesis—the division of a jail cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile band consisting of actin filaments and myosin Ii assembles merely underneath the plasma membrane. Its wrinkle pulls the plasma membrane progressively in, constricting the center of the jail cell and pinching information technology in two. Interestingly, the thickness of the contractile ring remains constant every bit it contracts, implying that actin filaments disassemble every bit wrinkle proceeds. The band then disperses completely following jail cell division.
Effigy 11.27
Cytokinesis. Post-obit completion of mitosis (nuclear sectionalisation), a contractile ring consisting of actin filaments and myosin II divides the jail cell in ii.
The regulation of actin-myosin contraction in striated muscle, discussed before, is mediated by the binding of Ca2+ to troponin. In nonmuscle cells and in shine musculus, even so, contraction is regulated primarily by phosphorylation of ane of the myosin light chains, called the regulatory low-cal concatenation (Figure 11.28). Phosphorylation of the regulatory low-cal concatenation in these cells has at least 2 effects: Information technology promotes the associates of myosin into filaments, and it increases myosin catalytic action, enabling wrinkle to proceed. The enzyme that catalyzes this phosphorylation, chosen myosin calorie-free-chain kinase, is itself regulated by association with the Caii+-binding protein calmodulin. Increases in cytosolic Ca2+ promote the binding of calmodulin to the kinase, resulting in phosphorylation of the myosin regulatory light concatenation. Increases in cytosolic Catwo+ are thus responsible, albeit indirectly, for activating myosin in smoothen muscle and nonmuscle cells, besides equally in striated muscle.
Effigy eleven.28
Regulation of myosin by phosphorylation. Caii+ binds to calmodulin, which in plough binds to myosin calorie-free-concatenation kinase (MLCK). The active calmodulin-MLCK complex then phosphorylates the myosin II regulatory low-cal chain, converting myosin from an inactive (more...)
Unconventional Myosins
In addition to myosin 2 ("conventional" 2-headed myosin), several other types of myosin are establish in nonmuscle cells. In contrast to myosin Ii, these "unconventional" myosins practice not form filaments and therefore are not involved in contraction. They may, however, exist involved in a multifariousness of other kinds of cell movements, such as the transport of membrane vesicles and organelles forth actin filaments, phagocytosis, and extension of pseudopods in amoebae (come across Figure 11.17).
The best-studied of these unconventional myosins are members of the myosin I family (Figure eleven.29). The myosin I proteins contain a globular head group that acts equally a molecular motor, like that of myosin II. However, members of the myosin I family are much smaller molecules (nearly 110 kd in mammalian cells) that lack the long tail of myosin II and do not form dimers. Their tails tin instead demark to other structures, such every bit membrane vesicles or organelles. The move of myosin I forth an actin filament tin can then transport its attached cargo. One function of myosin I, discussed earlier, is to form the lateral artillery that link actin bundles to the plasma membrane of abdominal microvilli (see Figure eleven.sixteen). In these structures, the motor activity of myosin I may move the plasma membrane along the actin bundles, toward the tip of the microvillus. Additional functions of myosin I may be in the ship of vesicles and organelles forth actin filaments and in motility of the plasma membrane during phagocytosis and pseudopod extension.
Figure eleven.29
Myosin I. Myosin I contains a head group similar to myosin Ii, but it has a comparatively brusk tail and does not form dimers or filaments. Although it cannot induce wrinkle, myosin I can move along actin filaments (toward the plus end), carrying (more than...)
In addition to myosins I and 2, at least 12 other classes of unconventional myosins (III through 14) have been identified. Some of these anarchistic myosins are 2-headed like myosin II, whereas others are one-headed like myosin I. The functions of most of these unconventional myosins remain to exist adamant, but some have been clearly shown to play important roles in organelle movement (myosins 5 and Half-dozen) and in sensory functions such as vision (myosin Iii) and hearing (myosins VI and Vii).
Jail cell Itch
The crawling movements of cells across a surface represent a basic form of prison cell locomotion, employed by a broad variety of different kinds of cells. Examples include the movements of amoebas, the migration of embryonic cells during development, the invasion of tissues by white blood cells to fight infection, the migration of cells involved in wound healing, and the spread of cancer cells during the metastasis of cancerous tumors. Similar types of movement are also responsible for phagocytosis and for the extension of nerve jail cell processes during evolution of the nervous system. All of these movements are based on the dynamic properties of the actin cytoskeleton, although the detailed mechanisms involved remain to be fully understood.
Cell itch involves a coordinated cycle of movements, which can exist viewed in iii stages. Showtime, protrusions such as pseudopodia, lamellipodia, or microspikes (encounter Figure eleven.17) must be extended from the leading edge of the cell (Figure 11.30). 2nd, these extensions must adhere to the substratum beyond which the cell is migrating. Finally, the trailing border of the prison cell must dissociate from the substratum and retract into the cell body.
Figure 11.30
Cell crawling. The crawling movements of cells beyond a surface can be viewed as three stages of coordinated movements: (1) extension of the leading edge, (ii) attachment of the leading edge to the substratum, and (3) retraction of the rear of the cell (more...)
A diversity of experiments indicate that extension of the leading edge involves the polymerization and crosslinking of actin filaments. For example, inhibition of actin polymerization (e.g., past treatment with cytochalasin) blocks the formation of prison cell surface protrusions. The regulated turnover of actin filaments, as illustrated in Figure 11.5, leads to the extension of processes such as filopodia and lamellipodia at the leading edge of the cell, and both cofilin and Arp2/3 proteins appear to exist involved in this procedure. Anarchistic myosins may also participate in the extension of processes at the leading edge: Myosin I is required for pseudopod extension in the amoeba Dictyostelium and Myosin V for extension of filopodia in neurons.
Post-obit their extension, protrusions from the leading edge must attach to the substratum in lodge to office in cell locomotion. For irksome-moving cells, such as fibroblasts, attachment involves the formation of focal adhesions (meet Figure xi.13). Cells moving more rapidly, such as amoebas or white blood cells, class more diffuse contacts with the substratum, the molecular composition of which is non known.
The third stage of cell crawling, retraction of the abaft edge, is the least understood. The attachments of the trailing border to the substratum are cleaved, and the rear of the prison cell recoils into the prison cell body. The process appears to require the evolution of tension between the forepart and rear of the cell, generating contractile force that eventually pulls the rear of the prison cell forward. This aspect of cell locomotion is impaired in mutants of Dictyostelium lacking myosin II, consistent with a function for myosin Ii in contracting the actin cortex and generating the force required for retraction of the trailing border.
Source: https://www.ncbi.nlm.nih.gov/books/NBK9961/
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