Dynamic instability causes microtubules
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Dynamic instability causes microtubules
These are questions and answers all of them have the right answers, I need you to paraphrase and shorten the answers as possible but not to lose the significant information.
2-Why do you suppose it is much easier to add tubulin to existing microtubules than to start a new microtubule from scratch? Explain how γ-tubulin in the centrosome helps to overcome this hurdle
Two tubulin dimers have a lower affinity for each other (because of a more limited number of interaction sites) than a tubulin dimer has for the end of a microtubule (where there are multiple possible interaction sites, both end-to-end of tubulin dimers adding to a protofilament and side-to-side of the tubulin dimers interacting with tubulin subunits in adjacent protofilaments forming the ringlike cross section). Thus, to initiate a microtubule from scratch, enough tubulin dimers have to come together and remain bound to one another for long enough for other tubulin molecules to add to them. Only when a number of tubulin dimers have already assembled will the binding of the next subunit be favored. The formation of these initial “nucleating sites” is therefore rare and will not occur spontaneously at cellular concentrations of tubulin. Centrosomes contain preassembled rings of γ-tubulin (in which the γ-tubulin subunits are held together in much tighter side-to-side interactions than αβ-tubulin can form) to which αβ-tubulin dimers can bind. The binding conditions of αβ-tubulin dimers resemble those of adding to the end of an assembled microtubule. The γ-tubulin rings in the centrosome can therefore be thought of as permanently preassembled nucleation sites.
3- Dynamic instability causes microtubules either to grow or to shrink rapidly. Consider an individual microtubule that is in its shrinking phase.
- What must happen at the end of the microtubule in order for it to stop shrinking and to start growing again?
The microtubule is shrinking because it has lost its GTP cap, i.e., the tubulin subunits at its end are all in their GDP-bound form. GTP-loaded tubulin subunits from solution will still add to this end, but they will be short-lived—either because they hydrolyze their GTP or because they fall off as the microtubule rim around them disassembles. If, however, enough GTP-loaded subunits are added quickly enough to cover up the GDPcontaining tubulin subunits at the microtubule end, a new GTP cap can form and regrowth is favored.
- How would a change in the tubulin concentration affect this switch?
The rate of addition of GTP-tubulin will be greater at higher tubulin concentrations. The frequency with which shrinking microtubules switch to the growing mode will therefore increase with increasing tubulin concentration. The consequence of this regulation is that the system is self-balancing: the more microtubules shrink (resulting in a higher concentration of free tubulin), the more frequently microtubules will start to grow again. Conversely, the more microtubules grow, the lower the concentration of free tubulin will become and the rate of GTP-tubulin addition will slow down; at some point GTP hydrolysis will catch up with new GTP-tubulin addition, the GTP cap will be destroyed, and the microtubule will switch to the shrinking mode.
- What would happen if only GDP, but no GTP, were present in the solution? If only GDP were present, microtubules would continue to shrink and eventually disappear, because tubulin dimers with GDP have very low affinity for each other and will not add stably to microtubules.
- What would happen if the solution contained an analog of GTP that cannot be hydrolyzed? If GTP is present but cannot be hydrolyzed, microtubules will continue to grow until all free tubulin subunits have been used up.
11- Which of the following statements are correct? Explain your answers.
- Kinesin moves endoplasmic reticulum membranes along microtubules so that the network of ER tubules becomes stretched throughout the cell.
True. A continual outward movement of ER is required; in the absence of microtubules, the ER collapses toward the center of the cell.
- Without actin, cells can form a functional mitotic spindle and pull their chromosomes apart but cannot divide.
True. Actin is needed to make the contractile ring that causes the physical cleavage between the two daughter cells, whereas the mitotic spindle that partitions the chromosomes is composed of microtubules.
- Lamellipodia and filopodia are “feelers” that a cell extends to find anchor points on the substratum that it will then crawl over.
True. Both extensions are associated with transmembrane proteins that protrude from the plasma membrane and enable the cell to form new anchor points on the substratum.
- GTP is hydrolyzed by tubulin to cause the bending of flagella.
False. To cause bending, ATP is hydrolyzed by the dynein motor proteins that are attached to the outer microtubules in the flagellum.
- Cells having an intermediate-filament network that cannot be depolymerized would die.
False. Cells could not divide without rearranging their intermediate filaments, but many terminally differentiated and long-lived cells, such as nerve cells, have stable intermediate filaments that are not known to depolymerize.
- The plus ends of microtubules grow faster because they have a larger GTP cap.
False. The rate of growth is independent of the size of the GTP cap. The plus and minus ends have different growth rates because they have physically distinct binding sites for the incoming tubulin subunits; the rate of addition of tubulin subunits differs at the two ends.
17-The drug Taxol, extracted from the bark of yew trees, has an opposite effect to the drug colchicine, an alkaloid from autumn crocus. Taxol binds tightly to microtubules and stabilizes them; when added to cells, it causes much of the free tubulin to assemble into microtubules. In contrast, colchicine prevents microtubule formation. Taxol is just as pernicious to dividing cells as colchicine, and both are used as anticancer drugs. Based on your knowledge of microtubule dynamics, suggest why both drugs are toxic to dividing cells despite their opposite actions.
Cell division depends on the ability of microtubules both to polymerize and to depolymerize. This is most obvious when one considers that the formation of the mitotic spindle requires the prior depolymerization of other cellular microtubules to free up the tubulin required to build the spindle. This rearrangement is not possible in Taxol-treated cells, whereas in colchicine-treated cells, division is blocked because a spindle cannot be assembled. On a more subtle but no less important level, both drugs block the dynamic instability of microtubules and would therefore interfere with the workings of the mitotic spindle, even if one could be properly assembled.
21-The locomotion of fibroblasts in culture is immediately halted by the drug cytochalasin, whereas colchicine causes fibroblasts to cease to move directionally and to begin extending lamellipodia in seemingly random directions. Injection of fibroblasts with antibodies to vimentin has no discernible effect on their migration. What do these observations suggest to you about the involvement of the three different cytoskeletal filaments in fibroblast locomotion?
Cytochalasin interferes with actin filament formation, and its effect on the cell demonstrates the importance of actin to cell locomotion. The experiment with colchicine shows that microtubules are required to give a cell a polarity that then determines which end becomes the leading edge. In the absence of microtubules, cells still go through the motions normally associated with cell movement, such as the extension of lamellipodia, but in the absence of cell polarity these are futile exercises because they happen indiscriminately in all directions. Antibodies bind tightly to the antigen (in this case vimentin) to which they were raised. When bound, an antibody can interfere with the function of the antigen by preventing it from interacting properly with other cell components. The antibody injection experiment therefore suggests that intermediate filaments are not required for the maintenance of cell polarity or for the motile machinery.