Where Do The Microtubules Of The Spindle Originate During Mitosis In Animal Cells

The segregation of the replicated chromosomes is brought about by a complex cytoskeletal motorcar with many moving parts—the mitotic spindle. It is constructed from microtubules and their associated proteins, which both pull the daughter chromosomes toward the poles of the spindle and move the poles apart.

As we have seen, the spindle starts to grade exterior the nucleus while the chromosomes are condensing during prophase. When the nuclear envelope breaks downwardly at prometaphase, the microtubules of the spindle are able to capture the chromosomes, which eventually get aligned at the spindle equator, forming the metaphase plate (see Console 18-ane). At anaphase, the sister chromatids abruptly separate and are fatigued to reverse poles of the spindle; at about the same time, the spindle elongates, increasing the separation between the poles. The spindle continues to elongate during telophase, equally the chromosomes arriving at the poles are released from the spindle microtubules and the nuclear envelope re-forms around them.

Both the assembly and the office of the mitotic spindle depend on microtubule-dependent motor proteins. As discussed in Chapter 16, these proteins belong to 2 families—the kinesin-related proteins, which unremarkably move toward the plus finish of microtubules, and the dyneins, which move toward the minus end. In the mitotic spindle, the motor proteins operate at or near the ends of the microtubules. These ends are not but sites of microtubule assembly and disassembly; they are also sites of force production. The assembly and dynamics of the mitotic spindle rely on the shifting residual between opposing plus-end-directed and minus-terminate-directed motor proteins.

3 classes of spindle microtubules can be distinguished in mitotic animal cells (Effigy 18-10). Astral microtubules radiate in all directions from the centrosomes and are thought to contribute to the forces that dissever the poles. They also act as "handles" for orienting and positioning the spindle in the cell. Kinetochore microtubules attach end-on to the kinetochore, which forms at the centromere of each duplicated chromosome. They serve to attach the chromosomes to the spindle. Overlap microtubules interdigitate at the equator of the spindle and are responsible for the symmetrical, bipolar shape of the spindle. All three classes of microtubules take their plus ends projecting away from their centrosome. The behavior of each grade is thought to exist unlike considering of the different poly peptide complexes that are associated with their plus and minus ends.

Figure 18-10

The three classes of microtubules of the fully formed mitotic spindle in an creature cell. (A) In reality, the chromosomes are proportionally much larger than shown in this drawing, and multiple microtubules are fastened to each kinetochore. Notation that the (more...)

Microtubule Instability Increases Greatly at M Phase

The mitotic spindle begins to self-assemble in the cytoplasm during prophase. In animal cells, each of the replicated centrosomes nucleates its ain array of microtubules, and the two sets of microtubules interact to class the mitotic spindle. We encounter later that the cocky-associates process depends on a rest between opposing forces that originate within the spindle itself and are generated past motor proteins associated with the spindle microtubules.

Many animal cells in interphase contain a cytoplasmic array of microtubules radiating out from the single centrosome. As discussed in Chapter xvi, the microtubules of this interphase assortment are in a country of dynamic instability, in which individual microtubules are either growing or shrinking and stochastically switch between the two states. The switch from growth to shrinkage is called a catastrophe, and the switch from shrinkage to growth is called a rescue (see Figure 16-eleven). New microtubules are continually being created to balance the loss of those that disappear completely past depolymerization.

Prophase signals an sharp alter in the jail cell's microtubules. The relatively few, long microtubules of the interphase array apace convert to a larger number of shorter and more dynamic microtubules surrounding each centrosome, which will begin to form the mitotic spindle. During prophase, the half-life of microtubules decreases dramatically. This can be seen by labeling the microtubules in living cells with fluorescent tubulin subunits (Figure 18-11). Equally the instability of microtubules increases, the number of microtubules radiating from the centrosomes greatly increases every bit well, patently because of an amending in the centrosomes themselves that increases the rate at which they nucleate new microtubules. How does the cell-cycle control system trigger these dramatic changes in the cell'due south microtubules at the onset of mitosis?

Figure 18-11

The one-half-life of microtubules in mitosis. Microtubules in an M-stage cell are much more than dynamic, on boilerplate, than the microtubules at interphase. Mammalian cells in culture were injected with tubulin that had been covalently linked to a fluorescent dye. (more than...)

Chiliad-Cdk initiates the changes by causing the phosphorylation of two classes of proteins that control microtubule dynamics (discussed in Chapter 16). These include microtubule motor proteins and microtubule-associated proteins (MAPs). The roles of these regulators in decision-making microtubule dynamics take been revealed past experiments using Xenopus egg extracts, which reproduce many of the changes that occur in intact cells during Grand phase. If centrosomes and fluorescent tubulin are mixed with extracts made from either M-phase or interphase cells, fluorescent microtubules nucleate from the centrosomes, permitting the beliefs of private microtubules to be analyzed by time-lapse fluorescence video microscopy. The microtubules in mitotic extracts differ from those in interphase extracts primarily past the increased rate of catastrophes, where they switch abruptly from slow growth to rapid shortening.

Proteins called catastrophins destabilize microtubule arrays by increasing the frequency of catastrophes (see Figure 16-36A). Among the catastrophins is a kinesin-related protein that does non function as a motor. In general, MAPs accept the opposite effect of catastrophins, stabilizing microtubules in various means: they can increase the frequency of rescues, in which microtubules switch from shrinkage to growth, or they can either increment the growth charge per unit or decrease the shrinkage rate of microtubules. Thus, in principle, changes in catastrophins and MAPs can make microtubules much more dynamic in Chiliad phase by increasing total microtubule depolymerization rates, decreasing total microtubule polymerization rates, or both.

In Xenopus egg extracts, the residue between a single type of catastrophin and a single blazon of MAP tin can be shown to determine the catastrophe rate and the steady-state length of microtubules. This residue, in turn, governs the assembly of the mitotic spindle, equally microtubules that are either also long or too short are incapable of assembling into a spindle (Figure 18-12). One way in which M-Cdk may control microtubule length is by phosphorylating this MAP and reducing its power to stabilize microtubules. Even if the activeness of the catastrophin remained constant throughout the cell bike, the residual between the 2 opposing activities of the MAP and catastrophin would shift, increasing the dynamic instability of the microtubules.

Effigy 18-12

Experimental testify that the residue between catastrophins and MAPs influences the frequency of microtubule catastrophes and microtubule length. (A) Interphase or mitotic Xenopus egg extracts were incubated with centrosomes, and the beliefs of individual (more...)

The cell contains a variety of MAPs, catastrophins, and motor proteins, each with subtly dissimilar activities. It is the balance between the opposing activities of these proteins that is responsible for the dynamic behavior of the mitotic spindle. We meet after how changes in this residual aid the spindle to segregate the chromosomes at anaphase.

Interactions Between Opposing Motor Proteins and Microtubules of Opposite Polarity Drive Spindle Assembly

While a shift in the balance betwixt MAPs and catastrophins early in Thousand stage creates more dynamic microtubules, a unlike sort of residuum, betwixt minus-end-directed and plus-finish-directed motor proteins, helps assemble the mitotic spindle. Because some of these motor proteins course oligomers that can cross-link next microtubules, they can move one microtubule relative to the other, with the direction of motion dependent on the polarity of both the motor poly peptide and the microtubules. In this way, these motor proteins can course foci by bringing together a group of microtubule ends (Figure eighteen-13A). Alternatively, such motor proteins tin can slide antiparallel microtubules past each other (Figure eighteen-13B). These two different motor protein functions play a crucial part in the assembly and function of the spindle: they create the foci of microtubule minus ends that form the two spindle poles, and they slide antiparallel microtubules past each other in the overlap zone of the spindle (see Figure xviii-10).

Figure 18-13

Two functions of multimeric motor proteins that are important for mitotic spindle assembly and function. Microtubule-dependent motor proteins hydrolyze ATP and move along a microtubule toward either its plus or its minus end. If the motor protein is multimeric, (more...)

During prophase in animal cells, microtubules growing from i centrosome engage with the microtubules of the side by side centrosome. Because the plus ends of the microtubules are oriented away from the centrosomes, these 2 sets of microtubules have opposite polarities. Plus-stop-directed motor proteins cantankerous-link the two sets of microtubules and help button the centrosomes autonomously to begin to form the two poles of the mitotic spindle (Figure eighteen-14). A balance between plus-end-directed motor proteins and minus-end-directed motor proteins is crucial for spindle assembly: whereas plus-end-directed motor proteins operating on overlap microtubules tend to push the 2 halves of the spindle apart, some minus-terminate-directed motor proteins tend to pull them together.

Figure eighteen-xiv

Separation of the 2 spindle poles in prophase in an animate being cell. In this model, plus-end-directed motor proteins operating on interacting antiparallel microtubules help split up the two poles of a forming mitotic spindle. New microtubules grow out in (more...)

At least vii families of kinesin-related motor proteins have been localized to the mitotic spindle in vertebrate cells. In the budding yeast S. cerevisiae, five such motor proteins have been shown to work together in the spindle. Increasing the level of i of the plus-end-directed motor proteins produces abnormally long spindles, whereas increasing the level of ane of the minus-stop-directed motor proteins produces abnormally short spindles (Figure 18-15). Thus, the balance between plus-end-directed and minus-terminate-directed motor proteins seems to determine spindle length. A similar balance betwixt motor proteins of reverse polarities occurs in man mitotic cells. At least, one of the motor proteins in human cells has to be phosphorylated by M-Cdk to bind to the spindle, suggesting i way in which K-Cdk might control the balance between opposing motor proteins.

Figure 18-15

The influence of opposing motor proteins on spindle length in budding yeast. (A) A differential-interference-contrast micrograph of a mitotic yeast cell. The spindle is highlighted in greenish, and the position of the spindle poles is indicated by red arrows. (more...)

Kinetochores Attach Chromosomes to the Mitotic Spindle

Prometaphase in animal cells begins abruptly with the breakdown of the nuclear envelope. The breakup is triggered when Thousand-Cdk directly phosphorylates the nuclear lamina that underlies the nuclear envelope (meet Effigy 12-20). The disassembly of the nuclear envelope allows the microtubules access to the condensed chromosomes for the commencement time. Now, the assembly of a mature mitotic spindle tin begin (see Panel 18-one, pp. 1034–1035).

The attachment of the chromosomes to the spindle is a dynamic procedure. When viewed by video microscopy, it seems to involve a "search and capture" mechanism, in which microtubules nucleated from each of the apace separating centrosomes grow outward toward the chromosomes. Microtubules that attach to a chromosome become stabilized, so that they no longer undergo catastrophes. They eventually end up attached end-on at the kinetochore, a complex protein motorcar that assembles onto the highly condensed Deoxyribonucleic acid at the centromere (discussed in Chapter four) during tardily prophase. The end-on zipper to the kinetochore is through the plus finish of the microtubule, which is now called a kinetochore microtubule (Figure 18-xvi).

Effigy xviii-xvi

Kinetochore microtubules. (A) A fluorescence micrograph of a metaphase chromosome stained with a Deoxyribonucleic acid-binding fluorescent dye and with human autoantibodies that react with specific kinetochore proteins. The ii kinetochores, one associated with each chromatid, (more...)

In newt lung cells, where the initial capture event can exist readily visualized, the kinetochore is seen kickoff to bind to the side of the microtubule and so to slide rapidly forth it toward 1 of the centrosomes. The lateral zipper to the chromosome is rapidly converted to an end-on attachment. At the same time, microtubules growing from the opposite spindle pole attach to the kinetochore on the contrary side of the chromosome, forming a bipolar attachment (Figure xviii-17). So begins a truly mesmerizing stage of mitosis. Get-go, the chromosomes are tugged dorsum and forth, eventually bold a position equidistant betwixt the two spindle poles, a position called the metaphase plate (Figure 18-xviii). In vertebrate cells, the chromosomes then oscillate gently at the metaphase plate, awaiting the signal to separate. The betoken is produced after a predictable lag time afterwards the bipolar attachment of the last of the chromosomes (discussed in Affiliate 17).

Effigy xviii-17

The capture of microtubules by kinetochores. The reddish arrow in (A) indicates the direction of microtubule growth, while the grey arrow in (C) indicates the direction of chromosome sliding.

Figure 18-18

Chromosomes at the metaphase plate of a mitotic spindle. In this fluorescence micrograph, kinetochores are labeled in red, microtubules in green, and chromosomes in blue. (From A. Desai, Curr. Biol. 10:R508, 2000. © Elsevier.)

Equally we discuss later, kinetochores play a crucial function in moving chromosomes on the spindle. They have a platelike organization when viewed in the electron microscope (Effigy xviii-19), and they are associated with both plus-cease-directed and minus-end-directed microtubule motor proteins. Merely it remains a mystery how the plus ends of microtubules are attached to the kinetochore, particularly because these ends are continuously polymerizing or depolymerizing, depending on the stage of mitosis.

Figure 18-19

The kinetochore. Electron micrograph of an anaphase chromatid with microtubules attached to its kinetochore. While most kinetochores have a trilaminar construction, the ane shown here (from a dark-green alga) has an unusually complex structure with additional (more...)

Microtubules Are Highly Dynamic in the Metaphase Spindle

The metaphase spindle is a circuitous and beautiful assembly, suspended in a state of dynamic equilibrium and tensed for activity that will begin in anaphase. All of the spindle microtubules, except the kinetochore microtubules, are in a state of dynamic instability, with their free plus ends shifting stochastically betwixt slow growth and rapid shrinkage. In addition, the kinetochore and overlap microtubules showroom a behavior called poleward flux, with a net improver of tubulin subunits at their plus end, balancing a net loss at their minus ends, near the spindle poles.

The poleward flux in kinetochore and overlap microtubules in metaphase spindles has been studied direct by allowing the microtubules to contain tubulin that has been covalently coupled to photoactivatable, "caged" fluorescein. When such spindles are marked with a beam of UV light from a light amplification by stimulated emission of radiation, the marks move continuously toward the spindle poles (Figure xviii-20). The fluorescent marks become dimmer with time, indicating that many of the overlap and kinetochore microtubules depolymerize completely and are replaced. The dynamics of individual spindle microtubules of all classes (astral, kinetochore, and overlap) tin can be studied by an ingenious method in which very depression amounts of fluorescent tubulin are injected into living cells (Figure 18-21). In these studies, a poleward flux is seen in both kinetochore and overlap microtubules, but not in astral microtubules. The part of the poleward flux, which does not occur in simple spindles such equally those in yeasts, is unknown, although it might aid chromosome movement in anaphase.

Effigy 18-20

The dynamic behavior of microtubules in the metaphase spindle studied past photoactivation of fluorescence. A metaphase spindle formed in vitro by adding Xenopus sperm to an extract of Xenopus eggs (see Figure 17-nine) has incorporated three fluorescent markers: (more...)

Effigy eighteen-21

Visualizing the dynamics of private microtubules past fluorescence speckle microscopy. (A) The principle of the method. A very depression amount of fluorescent tubulin is injected into living cells so that individual microtubules form with a very small proportion (more...)

One of the almost striking aspects of metaphase in vertebrate cells is the continuous oscillatory movement of the chromosomes at the metaphase plate. These movements have been studied by video microscopy in newt lung cells and are seen to switch between two states—a poleward (P) state, which is a minus-stop-directed pulling movement, and an away-from-the-pole (AP) state, which is a plus-end-directed movement. Kinetochores are thought to pull the chromosomes toward the poles, while an astral ejection strength is thought to push button the chromosomes abroad from the poles, toward the spindle equator (Figure xviii-22A). Plus-stop-directed motor proteins located on the chromosome arms are believed to interact with the astral microtubules to produce the ejection forcefulness (Figure 18-22B). Interestingly, spindles without centrosomes, including those in higher plants and some meiotic spindles, do non display these oscillations, which might reflect the absence of astral microtubules and, consequently, the absence of the astral ejection force.

Figure xviii-22

How opposing forces may bulldoze chromosomes to the metaphase plate. (A) Evidence for an astral ejection force that pushes chromosomes away from the spindle poles toward the spindle equator. In this experiment, a prometaphase chromosome that is temporarily (more than...)

Functional Bipolar Spindles Can Get together Around Chromosomes in Cells Without Centrosomes

Chromosomes are not just passive passengers in the process of spindle assembly. By creating a local environment that favors both microtubule nucleation and microtubule stabilization, they play an active part in spindle formation. The influence of the chromosomes tin can be demonstrated past using a fine glass needle to reposition them afterward the spindle has formed. For some cells in metaphase, if a single chromosome is tugged out of alignment, a mass of new spindle microtubules rapidly appears effectually the newly positioned chromosome, while the spindle microtubules at the chromosome's sometime position depolymerize. This property of the chromosomes seems to depend on a guanine-nucleotide exchange factor (Gef) that is spring to chromatin; information technology stimulates a small GTPase in the cytosol called Ran, inducing Ran to bind GTP in place of Gross domestic product. The activated Ran–GTP, which is too involved in nuclear transport (discussed in Chapter 12), releases microtubule-stabilizing proteins from poly peptide complexes in the cytosol, thereby stimulating the local nucleation of microtubules around chromosomes.

In cells without centrosomes, the chromosomes direct the assembly of a functional bipolar spindle. This is how spindles form in cells of higher plants, as well as in many meiotic cells. It is as well how they get together in sure insect embryos that have been induced to develop from eggs without fertilization (i.e., parthenogenetically); equally the sperm normally provides the centrosome when it fertilizes an egg (discussed in Chapter 20), the mitotic spindles in these parthenogenic embryos develop without centrosomes (Effigy eighteen-23). Remarkably, in artificial systems, spindles can self-assemble without either centrosomes or centromeres. When beads coated with DNA that lack centromere sequences (and therefore lack kinetochore complexes) are added to Xenopus egg extracts in the absence of centrosomes, bipolar spindles assemble around the beads (Figure 18-24A).

Figure 18-23

Bipolar spindle assembly without centrosomes in parthenogenetic embryos of the insect Sciara. The microtubules are stained green, the chromosomes carmine. The peak fluorescence micrograph shows a normal spindle formed with centrosomes in a usually fertilized (more than...)

Figure 18-24

Bipolar spindle assembly without centrosomes or kinetochores. (A) A fluorescence micrograph of a spindle (dark-green) that self-assembled around beads (ruby) coated with bacterial DNA in Xenopus egg extracts. (B) The steps in spindle assembly directed by Dna-coated (more...)

The centrosome-independent spindle assembly process is different from the assembly that is directed by centrosomes. In the DNA-coated bead model, for instance, the microtubules first nucleate near the surface of the Deoxyribonucleic acid, and then microtubule motor proteins sort the microtubules into bundles of uniform polarity, push the minus ends of the microtubules autonomously, and focus them into spindle poles (Figure 18-24B).

Even vertebrate cells can use such a centrosome-independent pathway to construct a functional bipolar spindle if the centrosomes are destroyed with a light amplification by stimulated emission of radiation beam. Although the resulting acentrosomal spindle tin can segregate chromosomes normally, it lacks astral microtubules, which are responsible for positioning the spindle in fauna cells; as a result, the spindle is oft mispositioned, resulting in abnormalities in cytokinesis. If present, nonetheless, centrosomes normally direct spindle associates because they are more efficient at nucleating microtubule polymerization than are chromosomes.

Anaphase Is Delayed Until All Chromosomes Are Positioned at the Metaphase Plate

Mitotic cells usually spend about half of M stage in metaphase, with the chromosomes aligned on the metaphase plate, jostling about, awaiting the signal that induces sister chromatids to separate to begin anaphase. Handling with drugs that destabilize microtubules, such equally colchicine or vinblastine (discussed in Chapter 16), arrests mitosis for hours or even days. This observation led to the identification of a spindle-attachment checkpoint, which is activated by the drug treatment and arrests progress in mitosis. The checkpoint mechanism is used by the cell-cycle control organization to ensure that cells do non enter anaphase until all chromosomes are fastened to both poles of the spindle (discussed in Chapter 17). If 1 of the protein components of the checkpoint mechanism is inactivated by mutation or by an intracellular injection of antibodies against the component, the cells initiate anaphase prematurely.

The spindle-zipper checkpoint monitors the zipper of the chromosomes to the mitotic spindle. It is thought to detect either unattached kinetochores or kinetochores that are non under the tension that results from bipolar zipper. In either instance, unattached kinetochores emit a signal that delays anaphase until they all are properly attached to the spindle (see Figure 17-27). Drugs that destabilize microtubules prevent such attachment and therefore maintain the signal and filibuster anaphase. The inhibitory signaling role of the kinetochore tin exist demonstrated in mammalian cells in culture, where a single unattached kinetochore can block anaphase; destruction of this kinetochore with a light amplification by stimulated emission of radiation causes the prison cell to enter anaphase.

Sister Chromatids Separate Suddenly at Anaphase

Anaphase begins abruptly with the release of the cohesin linkage that holds the sister chromatids together at the metaphase plate. Every bit discussed in Chapter 17, this metaphase-to-anaphase transition is triggered by the activation of the anaphase promoting complex (APC). Once this proteolytic complex is activated, it has at least 2 crucial functions: (1) it cleaves and inactivates the Thousand-phase cyclin (Chiliad-cyclin), thereby inactivating M-Cdk; and (2) it cleaves an inhibitory poly peptide (securin), thereby activating a protease called separase. Separase then cleaves a subunit in the cohesin circuitous to unglue the sis chromatids (encounter Figure 17-26). The sisters immediately separate—and are at present called daughter chromosomes—and move to reverse poles (Figure xviii-25).

Effigy eighteen-25

Chromatid separation at anaphase. In the transition from metaphase (A) to anaphase (B), sis chromatids all of a sudden separate and movement toward opposite poles—as shown in these light micrographs of Haemanthus (lily) endosperm cells that were stained (more...)

The chromosomes move past two independent and overlapping processes. The first, referred to as anaphase A, is the initial poleward movement of the chromosomes. It is accompanied past shortening of the kinetochore microtubules at their attachment to the chromosome and, to a lesser extent, by the depolymerization of spindle microtubules at the two spindle poles. The second process, referred to as anaphase B, is the separation of the poles themselves, which begins after the sister chromatids have separated and the daughter chromosomes have moved some distance apart. Anaphase A depends on motor proteins at the kinetochore. Anaphase B depends on motor proteins at the poles that pull the poles apart, as well as on motor proteins at the cardinal spindle (the bundles of antiparallel overlap microtubules between the separating chromosomes) that push the poles autonomously (Figure xviii-26). Originally, anaphase A and anaphase B were distinguished by their different sensitivities to drugs. These differences are at present thought to reverberate differences in the sensitivities of the microtubule motor proteins that mediate the ii processes.

Figure 18-26

The major forces that separate girl chromosomes at anaphase in mammalian cells. Anaphase A depends on motor proteins operating at the kinetochores that, together with the depolymerization of the kinetochore microtubules, pull the girl chromosomes (more...)

Kinetochore Microtubules Disassemble at Both Ends During Anaphase A

As each daughter chromosome moves poleward, its kinetochore microtubules depolymerize, and so that they have nearly disappeared at telophase. We tin see this process by fluorescence video microscopy, in which labeled tubulin is injected into cells then that the sites of contempo tubulin incorporation can be seen. In such experiments, the kinetochore ends of the kinetochore microtubules are observed to be the principal sites of tubulin addition during metaphase. In anaphase A, all the same, the kinetochore microtubules shorten mainly by the loss of tubulin from their kinetochore ends. It is not known how this switch from polymerization to depolymerization at kinetochores occurs at anaphase, but it may be triggered by the loss of tension that occurs when the cohesion between the sister chromatids is destroyed.

The poleward flux discussed earlier, with the continuous loss of tubulin subunits from both the overlap and kinetochore microtubules at the poles (see Figure 18-21), continues through anaphase. Thus, the kinetochore microtubules disassemble from both ends in anaphase.

Although it is clear that both microtubule motor proteins and microtubule depolymerization at the kinetochores contribute to chromosome movement during anaphase A, the exact molecular machinery that drives the movement is still unknown. It is also unclear how kinetochores can remain attached to a microtubule that is losing tubulin subunits at its kinetochore (plus) finish. In that location are two main ideas nigh how chromosomes move in anaphase A. Ane is that motor proteins at the kinetochores utilize the energy of ATP hydrolysis to pull the chromosomes forth the kinetochore microtubules, which depolymerize as a consequence. Another is that the depolymerization itself drives the movement, without using ATP (Figure xviii-27). The second possibility might seem implausible at first, but it has been shown that purified kinetochores in a examination tube, with no ATP present, can remain attached to depolymerizing microtubules and thereby motility. The energy that drives the movement is stored in the microtubule and is released when the microtubule depolymerizes; it ultimately comes from the hydrolysis of GTP that occurs after a tubulin subunit adds to the cease of a microtubule (discussed in Chapter sixteen). How motor proteins and microtubule depolymerization at the kinetochore combine to drive chromosome movement remains one of the fundamental mysteries of mitosis.

Effigy 18-27

Ii alternative models of how the kinetochore may generate a poleward forcefulness on its chromosome during anaphase A. (A) Microtubule motor proteins at the kinetochore use the energy of ATP hydrolysis to pull the chromosome along its bound microtubules. Depolymerization (more...)

Both Pushing and Pulling Forces Contribute to Anaphase B

In anaphase B, the spindle elongates, pulling the ii sets of chromosomes farther apart. In contrast to anaphase A, where the depolymerization of kinetochore microtubules is coupled to chromosome movement toward the poles, in anaphase B, the overlap microtubules actually elongate, helping to button the spindle poles apart. Anaphase B is driven by two distinct forces (see Figure 18-26). The first depends on plus-end-directed microtubule motor proteins in the fundamental spindle that form a bridge between the overlapping microtubules of contrary polarities; the translocation of these motors toward the microtubule plus ends slides the microtubules by one some other, pushing the poles autonomously. As a event, the bundle of overlap microtubules in the central spindle thins out (Figure 18-28). This mechanism is similar to that described earlier, in which motor proteins push button the poles apart during spindle assembly in prophase (see Figure eighteen-14). The 2d force contributing to anaphase B depends on minus-end-directed motor proteins that collaborate with both the astral microtubules and the cell cortex and pull the two poles of the spindle apart (Figure 18-29).

Figure 18-28

The sliding of overlap microtubules at anaphase. These electron micrographs prove the reduction in the degree of microtubule overlap in the cardinal spindle during mitosis in a diatom. (A) Metaphase. (B) Belatedly anaphase. (Courtesy of Jeremy D. Pickett-Heaps.) (more...)

Effigy 18-29

A model for how motor proteins may act in anaphase B. Plus-end-directed motor proteins cantankerous-link the overlapping, antiparallel, overlap microtubules and slide the microtubules past each other, thereby pushing the spindle poles apart. The red arrows indicate (more...)

The relative contributions of anaphase A and anaphase B to chromosome segregation vary greatly, depending on the cell type. In mammalian cells, anaphase B begins shortly after anaphase A and stops when the spindle is about twice its metaphase length; in contrast, the spindles of yeasts and certain protozoa primarily use anaphase B to split the chromosomes at anaphase, and their spindles elongate to up to 15 times the metaphase length in the process.

At Telophase, the Nuclear Envelope Re-forms Effectually Private Chromosomes

By the end of anaphase, the girl chromosomes have separated into two equal groups at opposite ends of the cell and have begun to decondense. In telophase, the final stage of mitosis, a nuclear envelope reassembles around each group of chromosomes to form the two daughter interphase nuclei.

The sudden transition from metaphase to anaphase initiates the dephosphorylation of the many proteins that were phosphorylated at prophase. Although the relevant phosphatases are active throughout mitosis, it is non until M-Cdk is switched off that the phosphatases tin act unopposed. Shortly thereafter, at telophase, nuclear membrane fragments associate with the surface of individual chromosomes and fuse to re-form the nuclear envelope. Initially, the fused membrane fragments partly enclose clusters of chromosomes; the fragments and so coagulate to re-form the complete nuclear envelope (see Figure 12-21). During this procedure, the nuclear pore complexes are incorporated into the envelope, and the dephosphorylated lamins reassociate to course the nuclear lamina. The nuclear envelope once again becomes continuous with the all-encompassing membrane sheets of the endoplasmic reticulum. Once the nuclear envelope has re-formed, the pore complexes pump in nuclear proteins, the nucleus expands, and the condensed mitotic chromosomes decondense into their interphase state, thereby assuasive cistron transcription to resume. A new nucleus has been created, and mitosis is complete. All that remains is for the jail cell to complete its division into two.

Summary

Mitosis begins with prophase, which is marked by an increase in microtubule instability, triggered by Thou-Cdk. In fauna cells, an unusually dynamic microtubule array (an aster) forms effectually each of the duplicated centrosomes, which divide to initiate the germination of the two spindle poles. Interactions between the asters and a balance between minus-terminate-directed and plus-end-directed microtubule-dependent motor proteins consequence in the self-assembly of the bipolar spindle. In college-plant cells and other cells that lack centrosomes, a functional, bipolar spindle self-assembles instead around the replicated chromosomes. Prometaphase begins with the breakdown of the nuclear envelope, which allows the kinetochores on the condensed chromosomes to capture and stabilize microtubules from each spindle pole. The kinetochore microtubules from opposite spindle poles pull in opposite directions on each duplicated chromosome, creating, together with a polar ejection force, a tension that helps bring the chromosomes to the spindle equator to grade the metaphase plate. The spindle microtubules at metaphase are highly dynamic and undergo a continuous poleward flux of tubulin subunits. Anaphase begins with the sudden proteolytic cleavage of the cohesin linkage holding sister chromatids together. The breakage of this linkage allows the chromosomes to be pulled to opposite poles (the anaphase A movement). At nearly the same time, the two spindle poles movement apart (the anaphase B motion). In telophase, the nuclear envelope re-forms on the surface of each group of separated chromosomes equally the proteins phosphorylated at the onset of M phase are dephosphorylated.

Source: https://www.ncbi.nlm.nih.gov/books/NBK26934/

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