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- W1970168250 abstract "What are microtubules? One of three types of protein polymer that make up the cellular cytoskeleton, an elaborate array of filaments that are used to establish cell shape, facilitate cell motility, organize organelles and assist with cell division. Microtubules are stiff tubes, about 25 nm in diameter. During interphase, they serve as tracks on which organelles and the nucleus are positioned by molecular motor proteins. During mitosis, microtubules form a structure called the mitotic spindle which physically segregates the chromosomes into the two daughter cells. What is microtubule dynamic instability? Microtubules have special dynamic properties. In a population of microtubules, at any point in time, a subset of microtubules are rapidly growing while others are quickly shrinking (although sometimes some microtubules also sit still in a ‘paused’ state). This intriguing property is explained by the observation that individual microtubules switch randomly between growing and shrinking states, sometimes changing back and forth several times in the course of their lifetime. This combination of growth, shrinkage and rapid transitions between the two is known as dynamic instability. Why is dynamic instability useful biologically? Speed. Dynamic instability allows the cell to rapidly reorganize the cytoskeleton when necessary. Dynamic microtubules are individually short-lived, so arrays of microtubules are continuously in the process of re-creation. Because microtubule growth and shrinkage are active processes, consuming energy, this turnover can be fast, on the order of minutes. This means that an array of microtubules can adapt quickly to changes in the environment, adopting new spatial arrangements in response to cellular needs. Examples include the reorganization of the cytoskeleton in the transition to mitosis and the extension of growth cones from neurons. How does dynamic instability work? Microtubules are made from subunits of the protein tubulin which are bound to the energy carrier guanosine triphosphate (GTP). The cell consumes energy to keep the concentration of GTP-tubulin high above the critical concentration for polymerization, far from equilibrium, so that subunits rapidly associate with microtubule ends and the microtubules grow. After subunits are incorporated into a microtubule, their GTP is hydrolyzed into GDP, releasing energy. It is believed that some of this energy goes to deform the tubulin subunit, changing it so it would be most stable in a curved state. This puts pressure on the microtubule to splay apart like a banana peeling. However, the GDP-tubulin is not free to curve outwards while it is trapped in the microtubule lattice — the curving can only begin at the ends. While the ends are stable, a microtubule will grow, but once an end begins to come apart, the splaying propagates down the microtubule (Figure 1). The energy stored in the tubulin subunits is released as the microtubule rapidly shrinks. What makes ends fall apart? We do not know what triggers ends to come apart. One possibility is that a layer of non-hydrolyzed, relatively stable GTP-tubulin remains at the microtubule end. In this case, the microtubule as a whole is stable and continues to grow. If this protective ‘cap’ is lost, the microtubule begins to splay. Alternatively, some other relatively rare ‘tearing’ event might begin microtubule shrinkage. So if dynamic instability consumes energy, can it do work? Yes! Growing microtubules can push against things, producing forces up to 4pN — comparable to the force produced by a kinesin motor, and enough to buckle the microtubules. Also, if the end of a shrinking microtubule is attached to an object, it can pull as it shrinks. In fact, microtubules attached to special sites on chromosomes are thought to use this type of force to pull the chromosomes apart during anaphase. How is dynamic instability regulated? Some microtubule-associated proteins, or MAPs, can attach along the sides of the microtubules, slowing or reversing shrinkage. These MAPs are dominant in interphase cells and neurons, which is why microtubules in these cells are not very dynamic. Other MAPs, dominant in mitosis, attach to microtubule ends, where they can stabilize or destabilize microtubules by changing the frequencies of transitions between growing and shrinking states. The activity of many of these MAPs is highly regulated in time and in space. Why is spatial regulation of dynamic instability important? Dynamic instability allows microtubules to rapidly explore space. If microtubules are preferentially stabilized or destabilized when they reach certain locations, the cell can build microtubule arrays with specific shapes. For example, during mitosis, selective stabilization of microtubules that encounter chromosomes is thought to help form the mitotic spindle." @default.
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- W1970168250 date "2006-07-01" @default.
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- W1970168250 title "Microtubule dynamic instability" @default.
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- W1970168250 doi "https://doi.org/10.1016/j.cub.2006.06.044" @default.
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